Ulcers are a disruption in the gastric mucosa (stomach and/or duodenum) greater than 5 mm, causing chronic inflammation. Chronic ulcers can be found anywhere in the gastrointestinal tract and are named according to their location or etiology (gastric or stress ulcers). Peptic ulcer disease, however, refers to those occurring in the stomach or duodenum.
An ulcer begins as a superficial erosion of the mucosa that is then subjected to the presence of pepsin and hydrochloric acid. The acid erodes the tissue as it attempts to heal itself and forms scar tissue at the base of what is now a developing ulcer. There is a decreased incidence of duodenal ulcers due to the eradication of Helicobacter pylori.

There are aggressive and defensive factors within the stomach and duodenum that balance each other to maintain a state of homeostasis. Aggressive forces are acid producers, whereas defensive forces are mucosal protectors. All people produce acid that is needed for digestion, but they can be separated into high, medium, or low acid producers. However, people who are high acid producers do not develop PUD at any greater rate than low acid producers. An imbalance between the aggressive and protective factors causes formation of an ulcer. Once considered a chronic disease, PUD is now thought to be caused by three major factors: H. pylori, nonsteroidal antiinflammatory drugs (NSAIDs), and Zollinger-Ellison syndrome. Other contributory risk factors include corticosteroid use, anticoagulants, cigarette smoking and alcohol abuse.