The most common causes of peptic ulcer disease (PUD) are Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). The test-and-treat strategy for detecting H. pylori is appropriate in situations where the risk of gastric cancer is low based on age younger than 55 years and the absence of alarm symptoms. Most other patients should undergo upper endoscopy to rule out malignancy and other serious causes of dyspepsia. Urea breath tests and stool antigen tests are most accurate for identifying H. pylori infection and can be used to confirm cure; serologic tests are a convenient but less accurate alternative and cannot be used to confirm cure. Treatment choices include standard triple therapy, sequential therapy, quadruple therapy, and levofloxacin-based triple therapy. Standard triple therapy is only recommended when resistance to clarithromycin is low. Chronic use of NSAIDs in patients with H. pylori infection increases the risk of PUD. Recommended therapies for preventing PUD in these patients include misoprostol and proton pump inhibitors. Complications of PUD include bleeding, perforation, gastric outlet obstruction, and gastric cancer. Older persons are at higher risk of PUD because of high-risk medication use, including antiplatelet drugs, warfarin, selective serotonin reuptake inhibitors, and bisphosphonates.