OBJECTIVES: To compare the cost-effectiveness of iv PPI (80mg bolus followed by 8mg/h infusion for 72 h) in patients considered at risk of gastric or duodenal ulcer (peptic ulcer) rebleeding after therapeutic endoscopy. METHODS: A systematic review and mixed treatment comparison (WinBUGS) provided estimates of the relative risk of peptic ulcer rebleed, repeat endoscopy and emergency surgery with acute iv PPI using placebo as a common comparator. A decision analytic model was then used to determine the cost per quality adjusted life years (QALYs) gained for iv esomeprazole, iv pantoprazole and iv omeprazole. Patients with no rebleed received 28-day treatment with the respective oral PPI (esomeprazole 40mg od, pantoprazole 40mg od or omeprazole 20mg od). Costs of medical and operative procedures were sourced from the National Schedule of Reference Costs (2007/08). Disutilities for repeat endoscopy and surgery were estimated from a published study that used time trade off interviews in adults with peptic ulcer disease. A 30-day time horizon was used. The analysis was conducted from the perspective of the UK National Health Service (NHS). Uncertainty was investigated through one way sensitivity analysis and probabilistic Monte Carlo simulation. RESULTS: Intravenous esomeprazole was the preferred treatment strategy. Probabilistic Monte Carlo simulation indicated that, at a threshold of £20,000/QALY, there was a 66% probability that iv esomeprazole was the most cost-effective compared to 33% and 1% for iv omeprazole or iv pantoprazole, respectively. The NHS would need to adopt a cost-effectiveness threshold in excess of £65,000/QALY for iv omeprazole to be considered the most cost-effective treatment for this indication. CONCLUSIONS: Based on the current best available evidence, iv esomeprazole, the only European licensed iv PPI for the prevention of recurrent peptic ulcer bleed after therapeutic endoscopy, is the most cost-effective treatment option and represents good value for money for the NHS.