OBJECTIVES: In recent clinical trials, esomeprazole, a new proton pump inhibitor, has been shown to be effective for long-term on demand treatment (medication taken as needed) to control recurrent symptoms in patients with Gastro-Oesophageal Reflux Disease (GORD) without oesophagitis. The objective of this analysis was to evaluate the cost-effectiveness of on demand treatment with esomeprazole, 20 mg, compared with intermittent treatment courses with omeprazole, 20 mg, od, or continuous omeprazole treatment following relapse in patients with GORD without oesophagitis. METHODS: A simple Markov model was designed to compare the cost-effectiveness of esomeprazole on demand treatment for six months with a strategy comprising intermittent treatment courses of omeprazole. In a further comparison, the strict intermittent omeprazole strategy was replaced by a strategy where continuous treatment was prescribed following a first relapse, which better reflects conventional care. Patient management was based on results from a UK physician survey of patient management in clinical practice. The UK survey results were adjusted for Finland and Sweden based on expert opinions. Direct medical costs in Finland, Sweden and the UK were used. Time with GORD, defined as weeks with symptoms during relapses, was used as the measure of effectiveness. RESULTS: Time with GORD was 0.4 weeks per patient in the esomeprazole on demand strategy, 2.2 weeks in the intermittent omeprazole strategy and 1.8 weeks in the conventional omeprazole strategy. The esomeprazole strategy incurred lower costs than either omeprazole strategy. This analysis represents a conservative estimate of the cost-effectiveness of on demand treatment with esomeprazole, since data from clinical trials using placebo plus antacids as rescue medication were used as a substitute for relapse in patients with GORD without oesophagitis