Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating. With a gastric ulcer, the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of cases.

Common causes include the bacteria Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Other, less common causes include tobacco smoking, stress as a result of other serious health conditions, Behçet's disease, Zollinger–Ellison syndrome, Crohn's disease, and liver cirrhosis. Older people are more sensitive to the ulcer-causing effects of NSAIDs. The diagnosis is typically suspected due to the presenting symptoms with confirmation by either endoscopy or barium swallow. H. pylori can be diagnosed by testing the blood for antibodies, a urea breath test, testing the stool for signs of the bacteria, or a biopsy of the stomach. Other conditions that produce similar symptoms include stomach cancer, coronary heart disease, and inflammation of the stomach lining or gallbladder inflammation.

Diet does not play an important role in either causing or preventing ulcers. Treatment includes stopping smoking, stopping use of NSAIDs, stopping alcohol, and taking medications to decrease stomach acid. The medication used to decrease acid is usually either a proton pump inhibitor (PPI) or an H2 blocker, with four weeks of treatment initially recommended. Ulcers due to H. pylori are treated with a combination of medications, such as amoxicillin, clarithromycin, and a PPI. Antibiotic resistance is increasing and thus treatment may not always be effective. Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.

Peptic ulcers are present in around 4% of the population. New ulcers were found in around 87.4 million people worldwide during 2015. About 10% of people develop a peptic ulcer at some point in their life. Peptic ulcers resulted in 267,500 deaths in 2015, down from 327,000 in 1990. The first description of a perforated peptic ulcer was in 1670, in Princess Henrietta of England. H. pylori was first identified as causing peptic ulcers by Barry Marshall and Robin Warren in the late 20th century, a discovery for which they received the Nobel Prize in 2005.