Background & Aims: The long-term prognosis of peptic ulcers associated with neither Helicobacter pylori nor nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. Methods: This 7-year prospective cohort study recruited patients with bleeding ulcers from January to December 2000. H pylori-negative idiopathic bleeding ulcers were defined as having tested negative for H pylori, having no exposure to aspirin or analgesics within 4 weeks before endoscopy, and having no other identifiable causative factors. After ulcers healed, patients were divided into 2 groups: patients with prior H pylori-negative idiopathic bleeding ulcers (H pylori-negative idiopathic ulcer cohort; n = 120) and those with H pylori-positive, NSAID-negative bleeding ulcers who received eradication therapy (H pylori ulcer cohort; n = 213). Both groups were followed for ≤7 years without gastroprotective therapy. The primary endpoints were recurrent ulcer bleeding and mortality. Results: The 7-year cumulative incidence of recurrent ulcer bleeding was 42.3% (95% CI, 36.5%-48.1%) in the H pylori-negative idiopathic ulcer cohort and 11.2% (95% CI, 8.8%-13.6%) in the H pylori ulcer cohort (a difference of 31.1%; 95% CI, 27.7%-34.5%; P < .0001). Significantly more patients died in the H pylori-negative idiopathic ulcer cohort (87.6%; 95% CI, 83.0%-92.2%) than in the H pylori ulcer cohort (37.3%; 95% CI, 34.0%-40.6%) with a difference of 50.3% (95% CI, 49.0%-51.6%; P < .0001). Conclusions: Patients with history of H pylori-negative idiopathic bleeding ulcers have a high risk of recurrent ulcer bleeding and mortality. © 2009 AGA Institute.