OBJECTIVES: Peptic ulcer bleeding (PUB) is a serious and life-threatening condition. Currently, no proton pump inhibitor has a label for being used in this setting. A recent multinational clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous esomeprazole (HIE), when administered after endoscopic haemostasis to patients with bleeding ulcers, is effective in preventing re-bleeding. METHODS: A decision-tree model was built, including patients with PUB following successful endoscopic haemostasis performed within 24 hours of initial presentation, comparing HIE (80mg infusion, then 8mg/h for 3 days) versus placebo, with both groups receiving oral esomeprazole 40mg daily from days 4 to 30. The model adopted a 30-day time horizon, using a Spanish third-party payer perspective. The outcome was the rate of averted re-bleeds. Probabilities and lengths of hospital stay were provided from the recent trial. Hospital costs, including physician fees, and data for other model assumptions were retrieved from the literature. RESULTS: Re-bleed rates were 7.7% (n=375) for HIE, and 13.6% (n=389) for the placebo group (p<0.01). The average costs per patient for the HIE and placebo strategies were €4924 and €4994, respectively. Thus, HIE was the dominant strategy (both more effective and less costly than placebo). Sensitivity analysis confirmed the robustness of the results, with the placebo strategy being less expensive only under specific circumstances (eg. when significantly varying re-bleed rates or dropping the hospitalization costs for patients with a re-bleed). CONCLUSIONS: Based on recent high-quality clinical trial data and modelling, the high-dose intravenous esomeprazole strategy was more effective and less costly than the placebo strategy.