Peptic Ulcer Disease: Causes, Symptoms, and Treatment

For decades, people blamed spicy food and stress for stomach ulcers. That myth was overturned in 1982, when two Australian researchers – Barry Marshall and Robin Warren, who later shared a Nobel Prize for the work – discovered that a bacterium, Helicobacter pylori, was the primary culprit behind most cases of peptic ulcer disease. Today we know that peptic ulcers affect several million Americans each year (older estimates put new cases around 4.6 million annually), and that the two leading causes are H. pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The good news: most peptic ulcers can be effectively treated, and many can be cured, when properly diagnosed. For context on how this condition fits among other common health concerns, see our medical conditions guide.

What Is Peptic Ulcer Disease?

A peptic ulcer is an open sore that develops on the inner lining of the stomach, the upper small intestine (duodenum), or, less commonly, the esophagus. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), peptic ulcers are classified by location: gastric ulcers form in the stomach, duodenal ulcers form in the first part of the small intestine, and esophageal ulcers form in the lower esophagus.

The stomach lining is normally protected by a thick layer of mucus that shields it from the corrosive effects of hydrochloric acid and digestive enzymes. When this protective barrier breaks down – whether from bacterial infection, medication use, or other factors – acid erodes the lining and creates an ulcer. These sores can range from a few millimeters to several centimeters in diameter.

Duodenal ulcers are more common than gastric ulcers, particularly in younger adults. Gastric ulcers tend to occur in people over age 50. While peptic ulcer disease was once considered a chronic, recurring condition that people simply had to live with, modern treatment – particularly the eradication of H. pylori – has transformed it into a largely curable disease for most patients.

Causes: H. pylori and NSAIDs

Helicobacter pylori is a spiral-shaped bacterium that has co-evolved with humans for tens of thousands of years. It colonizes the stomach lining, burrowing beneath the mucus layer where it triggers chronic inflammation. According to the Centers for Disease Control and Prevention (CDC), a large share of the world’s population carries H. pylori – roughly a third of adults in the United States by many estimates – though most infected individuals never develop ulcers. When ulcers do form from infection, H. pylori is responsible for the majority of gastric ulcers and the great majority of duodenal ulcers.

NSAIDs – including aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve) – are the second leading cause. These medications inhibit cyclooxygenase (COX) enzymes, which not only reduces pain and inflammation but also depletes prostaglandins that protect the stomach lining. Regular NSAID use increases ulcer risk several-fold. The risk rises further with higher doses, longer duration, concurrent use of corticosteroids, anticoagulants, or antiplatelet drugs, a prior ulcer, and older age – especially over 65. Because so many NSAIDs are sold over the counter, people often take them without realizing the cumulative risk.

Less common causes include Zollinger-Ellison syndrome (a rare condition in which tumors drive excessive acid production), severe physiologic stress from critical illness or major surgery, radiation therapy, and certain infections in immunocompromised patients. A minority of ulcers are truly “idiopathic” (no identifiable cause). Importantly, while psychological stress and dietary factors can worsen symptoms, they do not by themselves cause peptic ulcers.

Recognizing the Symptoms

The most characteristic symptom of peptic ulcer disease is a burning or gnawing pain in the upper abdomen, often described as an “empty” or “hungry” feeling. With duodenal ulcers, this pain typically occurs between meals and during the night, often improving temporarily after eating or taking antacids. Gastric ulcers, by contrast, may cause pain that worsens during or shortly after eating.

Other common symptoms include bloating, early satiety (feeling full after eating only a small amount), nausea, and belching. Some patients experience heartburn or acid reflux symptoms that overlap with GERD. Weight loss can occur with gastric ulcers if pain discourages eating. However, the Mayo Clinic notes that many people with peptic ulcers – particularly those caused by NSAIDs – have minimal or no symptoms until a complication such as bleeding occurs. That silent course is one reason NSAID-related ulcers can be dangerous.

Alarm features that warrant prompt medical evaluation and usually endoscopy include unintentional weight loss, difficulty or pain with swallowing, persistent vomiting, evidence of gastrointestinal bleeding, iron-deficiency anemia, a family history of upper-GI cancer, or new-onset symptoms after age 55 to 60. See the red-flag box above for the emergency signs that require calling 911 rather than waiting for an appointment.

How Peptic Ulcers Are Diagnosed

Diagnosis begins with a thorough history and physical examination. Your doctor will ask about NSAID and aspirin use, symptoms, and relevant medical history. Testing for H. pylori is a critical part of the evaluation. Several non-invasive tests are available: the urea breath test (you drink a solution and breathe into a bag), the stool antigen test, and a blood antibody test. The breath and stool tests are preferred because they detect active infection, whereas antibody tests can remain positive long after an infection has cleared. For accuracy, patients are usually asked to stop PPIs for a period and avoid recent antibiotics and bismuth before breath or stool testing.

Upper endoscopy (esophagogastroduodenoscopy, or EGD) is the gold standard for visualizing ulcers directly. During this procedure, a thin, flexible tube with a camera is passed through the mouth into the stomach and duodenum. The physician can assess the ulcer’s size, location, and characteristics, take biopsies to test for H. pylori and rule out malignancy, and even treat active bleeding. According to the American College of Gastroenterology (ACG), endoscopy is particularly recommended for patients with alarm features (weight loss, anemia, difficulty swallowing, bleeding), those with new-onset symptoms at an older age, and those who do not respond to initial treatment. Any gastric ulcer seen on endoscopy is typically biopsied and re-examined after healing to be sure it is not cancer.

For patients without alarm symptoms, particularly younger adults, a “test-and-treat” strategy may be used: test for H. pylori with a non-invasive method, and if positive, treat with an appropriate regimen without endoscopy. This approach is cost-effective and supported by clinical guidelines.

Treatment: Eradicating H. pylori

When H. pylori is identified, eradication is essential – it heals the ulcer, dramatically lowers the chance of recurrence, and reduces long-term cancer risk. Historically, the standard first-line regimen in the United States was a 14-day course of “triple therapy”: a proton pump inhibitor (PPI) plus two antibiotics, usually clarithromycin and amoxicillin. But rising resistance – particularly to clarithromycin – has made that combination unreliable in many parts of the country.

Reflecting this, the ACG’s updated guidance (its 2017 guideline and a further 2024 update) recommends moving away from empiric clarithromycin triple therapy unless local resistance is known to be low or the patient’s susceptibility has been tested. Current preferred first-line options a clinician may choose from include:

• Bismuth quadruple therapy – a PPI, bismuth subsalicylate, tetracycline, and metronidazole – which remains effective even where clarithromycin resistance is common.
• Rifabutin-based triple therapy – a PPI, amoxicillin, and rifabutin (available in the U.S. as a fixed-dose combination, Talicia) – a useful option because H. pylori resistance to rifabutin is rare.
• Vonoprazan-based therapy – vonoprazan (Voquezna) is a newer potassium-competitive acid blocker (PCAB) that suppresses stomach acid faster and more consistently than traditional PPIs. It is FDA-approved paired with amoxicillin (dual therapy) or with amoxicillin plus clarithromycin (triple therapy) for H. pylori, and has become an increasingly common first-line choice.

Eradication success rates vary by regimen, adherence, and local resistance patterns. After treatment, the ACG recommends confirming that the infection is cured, using a urea breath test or stool antigen test performed at least four weeks after finishing antibiotics and at least two weeks after stopping PPI or PCAB therapy. If the first regimen fails, a different combination that avoids previously used antibiotics is chosen – this is called “salvage” or “rescue” therapy. Because these regimens involve multiple drugs, precise choices and dosing must be individualized by a clinician; do not attempt to assemble an antibiotic regimen on your own, and take the full course exactly as prescribed.

Treatment: Acid Suppression and Mucosal Healing

Regardless of the underlying cause, acid suppression is a cornerstone of ulcer treatment. Proton pump inhibitors – omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), and others – are highly effective acid-suppressing medications. They block the hydrogen-potassium ATPase enzyme in the stomach’s parietal cells, sharply reducing acid secretion and allowing most ulcers to heal within 4 to 8 weeks. The newer potassium-competitive acid blocker vonoprazan offers an alternative mechanism with rapid, sustained acid control.

H2 receptor antagonists – famotidine (Pepcid), for example – are less potent but still useful, particularly for duodenal ulcers and milder disease. Antacids provide quick symptomatic relief but do not heal ulcers. Sucralfate, a mucosal protectant, coats the ulcer crater and provides a physical barrier against acid, though it is used less frequently today than PPIs.

For NSAID-induced ulcers, the single most important step is stopping the offending medication when it is safe to do so. If NSAID use must continue – as in some patients with rheumatoid arthritis or those who need low-dose aspirin for cardiovascular protection – a PPI should be prescribed at the same time to protect the stomach lining. COX-2 selective inhibitors such as celecoxib carry lower gastrointestinal risk than traditional NSAIDs but are not risk-free, especially when combined with aspirin. These trade-offs should be weighed with your clinician rather than managed alone.

Complications of Peptic Ulcer Disease

Untreated or poorly managed peptic ulcers can lead to several serious complications. Gastrointestinal bleeding is the most common, occurring in a meaningful minority of ulcer patients over their lifetime. Bleeding can be slow and chronic (leading to iron-deficiency anemia) or acute and life-threatening. According to the NIDDK, bleeding peptic ulcers account for a large number of hospitalizations in the United States each year.

Perforation occurs when an ulcer erodes completely through the stomach or duodenal wall, allowing digestive contents to leak into the abdominal cavity. This is a surgical emergency causing sudden, severe abdominal pain, a rigid abdomen, and rapid deterioration. Penetration – when an ulcer erodes into an adjacent organ such as the pancreas – causes persistent, often back-radiating pain.

Gastric outlet obstruction, though less common in the modern era, can develop when chronic inflammation and scarring narrow the pyloric channel or duodenum. Patients experience persistent vomiting, early satiety, and weight loss. Treatment may involve endoscopic balloon dilation or surgery. Long-standing H. pylori infection is also associated with an increased risk of gastric cancer and gastric MALT lymphoma – another reason eradication matters.

The Role of Lifestyle in Ulcer Management

While lifestyle factors do not cause peptic ulcers on their own, certain habits influence symptoms and healing. Smoking is the most important modifiable lifestyle risk factor – it impairs mucosal blood flow, inhibits protective bicarbonate secretion, and slows ulcer healing. Smokers have higher ulcer recurrence rates and increased complication risk, so quitting is strongly recommended for anyone with peptic ulcer disease.

Alcohol in excess can irritate and erode the stomach lining, worsening symptoms. Moderate alcohol consumption has not been definitively linked to increased ulcer risk, but during active disease, limiting or avoiding alcohol is prudent. Caffeine stimulates acid secretion and may aggravate symptoms in some individuals, though it has not been shown to cause ulcers or delay healing.

Eating smaller, more frequent meals may help manage symptoms, though there is no specific “ulcer diet” supported by strong evidence. The old recommendation to drink milk for ulcers has been debunked – milk briefly buffers acid but then stimulates additional acid production. Managing stress through healthy outlets, while not curative, can reduce symptom perception and improve quality of life. Understanding the financial aspects of treatment can also reduce anxiety about managing the condition.

When Surgery Is Needed

With effective PPIs, acid blockers, and H. pylori eradication therapy, surgery for peptic ulcer disease has become relatively rare. It remains necessary in certain situations: life-threatening bleeding that cannot be controlled endoscopically, perforation, gastric outlet obstruction unresponsive to endoscopic treatment, and ulcers strongly suspected of being malignant.

Surgical options depend on the specific complication and ulcer location. Procedures may include oversewing of a bleeding vessel, repair of a perforation with an omental patch, vagotomy (cutting the vagus nerve to reduce acid secretion), antrectomy (removal of the acid-producing portion of the stomach), or various drainage procedures. Minimally invasive laparoscopic techniques are increasingly used for ulcer surgery, offering shorter recovery times compared with open operations.

Post-surgical patients require long-term follow-up to monitor for complications such as dumping syndrome, bile reflux, and nutritional deficiencies, particularly vitamin B12 and iron. Fortunately, the need for ulcer surgery has declined dramatically over the past several decades thanks to effective medical therapy.

Frequently Asked Questions

Can stress cause a peptic ulcer?

Psychological stress alone does not cause peptic ulcers. The two proven causes are H. pylori infection and NSAID use. However, severe physiologic stress – from major surgery, critical illness, burns, or traumatic injuries – can cause “stress ulcers” in the stomach lining of hospitalized patients. Psychological stress may worsen existing ulcer symptoms and may contribute to behaviors (like increased NSAID use or smoking) that raise ulcer risk, but it is not an independent cause.

How long does it take for a peptic ulcer to heal?

With appropriate treatment – including acid suppression and, when applicable, H. pylori eradication – most peptic ulcers heal within 4 to 8 weeks. Duodenal ulcers generally heal faster (about 4 to 6 weeks) than gastric ulcers (about 6 to 8 weeks). Larger ulcers or those complicated by scarring may take longer. Following through with the full course of treatment is critical; stopping medication early because symptoms improve can lead to incomplete healing and recurrence.

Are peptic ulcers the same as stomach cancer?

No. Peptic ulcers are benign (non-cancerous) sores, and the vast majority remain benign. However, a gastric ulcer occasionally turns out to be cancerous, which is why physicians often biopsy gastric ulcers during endoscopy and perform a follow-up endoscopy to confirm healing. Duodenal ulcers are almost never malignant. Chronic H. pylori infection is a recognized risk factor for gastric cancer, which is one of many reasons eradication is recommended when infection is detected.

Can I take NSAIDs if I’ve had a peptic ulcer?

This requires careful discussion with your doctor. If you have had an NSAID-related ulcer, the safest approach is usually to avoid NSAIDs entirely and use acetaminophen (Tylenol) for pain instead, since it does not damage the stomach lining. If NSAIDs are medically necessary – for example, low-dose aspirin for heart protection – taking a daily PPI significantly reduces ulcer recurrence risk. A COX-2 selective inhibitor plus a PPI is another option that provides an added layer of gastroprotection. Do not start or stop aspirin or other prescribed medicines on your own; coordinate any change with your clinician.

Is H. pylori contagious?

Yes. H. pylori is transmitted from person to person, likely through oral-oral or fecal-oral routes. It is most commonly acquired during childhood, particularly in settings with crowded living conditions or limited sanitation. The infection persists for life unless treated with antibiotics. Routine testing and treatment of family members is not generally recommended unless they also have symptoms or related conditions such as ulcers or unexplained iron-deficiency anemia.

What has changed recently in H. pylori treatment?

The biggest shift is a move away from the old empiric clarithromycin triple therapy because of widespread antibiotic resistance. Updated U.S. guidance now favors bismuth quadruple therapy, rifabutin-based triple therapy (Talicia), and vonoprazan-based regimens as preferred first-line options in many situations, and it emphasizes confirming a cure after treatment. The best regimen depends on your antibiotic history, allergies, and local resistance patterns, so it should be chosen by your clinician.

Taking Control of Your Digestive Health

If you are experiencing persistent upper-abdominal pain, burning, or any of the symptoms described above, don’t dismiss them or self-treat indefinitely with over-the-counter antacids. Getting a proper diagnosis – including testing for H. pylori – is the most important step, because effective treatment depends on identifying the underlying cause.

For those already diagnosed with peptic ulcer disease, adherence to your treatment plan is essential. Complete the full course of prescribed medicine if H. pylori is present. Take your acid-suppressing medication as directed. If you use NSAIDs, discuss alternatives or gastroprotective strategies with your doctor. Quit smoking if you haven’t already, and be mindful of alcohol during the healing period.

The outlook for peptic ulcer disease is excellent with proper treatment. Eradicating H. pylori reduces ulcer recurrence from the high rates seen in the past to a small percentage. Most patients heal completely and return to normal eating and activity without restrictions. The key is not to delay – early diagnosis and targeted treatment prevent complications and lead to lasting relief.

Sources

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – Peptic Ulcers (Stomach Ulcers)
• Mayo Clinic – Peptic Ulcer: Symptoms and Causes
• Centers for Disease Control and Prevention (CDC) – Helicobacter pylori
• American College of Gastroenterology – Peptic Ulcer Disease patient resources and ACG Clinical Guideline on the Treatment of Helicobacter pylori Infection (2017; 2024 update)
• MedlinePlus (U.S. National Library of Medicine) – Peptic Ulcer
• U.S. Food and Drug Administration / DailyMed – vonoprazan (Voquezna) and rifabutin-amoxicillin-omeprazole (Talicia) prescribing information