BACKGROUND: Management of peptic ulcer disease has improved over the past few decades: However, the widespread use of nonsteroidal anti-inflammatory drugs and low-dose acetylsalicylic acid means that the burden of peptic ulcer disease remains a relevant issue. METHODS: We systematically searched PubMed and EMBASE for articles published 1966-2007 that reported symptoms, impairment of well-being or health-related quality of life, and costs associated with peptic ulcer disease. RESULTS: Thirty studies reported the prevalence of patient-reported gastrointestinal symptoms in individuals with endoscopically diagnosed symptomatic peptic ulcer disease. Average prevalence estimates, weighted by sample size, were 81% (95% confidence.interval [CI], 77%-85%) for abdominal pain (11 studies), 81% (95% CI, 76%-85%) for pain specifically of epigastric origin (14 studies), and 46% (95% CI, 42%-50%) for heartburn or acid regurgitation (11 studies). On average, 29% (95% CI, 25%-34%) of patients with peptic ulcer disease presented with bleeding, often as the initial symptom (11 studies). Patients with peptic ulcer disease had significantly lower health-related quality of life than the general population, as measured by the Psychological General Well-Being index (P < .05; 7 studies) and the Short-Form-36 questionnaire (P < .05; 2 studies). Direct medical costs of peptic ulcer disease based on national estimates from several countries were USD163-866 per patient. The most costly aspects of peptic ulcer disease management were hospitalization and medication. Complicated peptic ulcer disease is particularly costly, estimated to be USD1883-25,444 per patient. CONCLUSION: Peptic ulcer disease significantly impairs well-being and aspects of health-related quality of life, and is associated with high costs for employers and health care systems. (C) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 358-366