Objective: Patients with a history of Helicobacter pylori -negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications. We hypothesised that a proton pump inhibitor (lansoprazole) is superior to a histamine 2 receptor antagonist (famotidine) for the prevention of recurrent ulcer bleeding in such patients., Design: In this industry-independent, double-blind, randomised trial, we recruited patients with a history of idiopathic bleeding ulcers. After ulcer healing, we randomly assigned (1:1) patients to receive oral lansoprazole 30 mg or famotidine 40 mg daily for 24 months. The primary endpoint was recurrent upper GI bleeding within 24 months, analysed in the intention-to-treat population as determined by an independent adjudication committee., Results: Between 2010 and 2018, we enrolled 228 patients (114 patients in each study group). Recurrent upper GI bleeding occurred in one patient receiving lansoprazole (duodenal ulcer) and three receiving famotidine (two gastric ulcers and one duodenal ulcer). The cumulative incidence of recurrent upper GI bleeding in 24 months was 0.88% (95% CI 0.08% to 4.37%) in the lansoprazole arm and 2.63% (95% CI 0.71% to 6.91%) in the famotidine arm (p = 0.313; crude HR 0.33, 95% CI 0.03 to 3.16, p = 0.336). None of the patients who rebled used aspirin, non-steroidal anti-inflammatory drugs or other antithrombotic drugs., Conclusion: This 2-year, double-blind randomised trial showed that among patients with a history of H. pylori -negative idiopathic ulcer bleeding, recurrent bleeding rates were comparable between users of lansoprazole and famotidine, although a small difference in efficacy cannot be excluded., Trial Registration Number: NCT01180179; Results., Competing Interests: Competing interests: GL-HL-HW has served as a speaker for Abbott, AbbVie, Bristol-Myers Squibb, Echosens, Gilead and Janssen, and an advisory committee member for Gilead and Janssen. VW-SW has served as a speaker for AbbVie, Bristol-Myers Squibb, Roche, Novartis, Abbott Diagnostics and Echosens, and an advisory committee member for AbbVie, Roche, Novartis, Gilead and Otsuka. PWYC has served as a speaker for Olympus and an advisory committee member for EndoMASTER and Aptorum. JL has served as a speaker for Boston Scientific. FKLC has served as a consultant to Eisai, Pfizer, Takeda and Otsuka, and has been paid lecture fees by Eisai, Pfizer, AstraZeneca and Takeda., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)