OBJECTIVES: On-demand proton pump inhibitor (PPI) maintenance therapy is recommended for patients with symptomatic gastroesophageal reflux disease (GERD) in Italy who achieve symptom remission after 4 weeks of continuous treatment. The objectives of this analysis are to evaluate the costs to the health care system (NHS) and to society and effectiveness (quality adjusted life years) of on-demand maintenance therapy in patients with symptomatic GERD. METHODS: Decision analysis and Markov modelling of costs and effectiveness up to 12 months. Efficacy data were extracted from seven placebo-controlled trials; the primary outcome measure was time to treatment discontinuation owing to relapse of symptoms, requiring continuous therapy. Health state utilities were derived from a previously published study and data on health care resource utilisation were obtained from a prospective Italian study that followed 577 patients with functional dyspepsia for one year. RESULTS: Differences in utility scores associated with each PPI, ranging from 0.731 to 0.745 quality-adjusted life years, were not statistically different. Annual expected cost, however, were statistically different among the different drugs and the following cost-minimization raking was obtained for costs to the NHS and to society, respectively: rabeprazole (181€, 295€), pantoprazole (223€, 341€), lansoprazole (249€, 370€), omeprazole 10 mg (297€, 412€), esomeprazole (295€, 419€), omeprazole 20 mg (405€, 528€). Unit cost of PPI was the major determinant of cost to the NHS, while productivity days lost due to symptoms was the major determinant of cost to society. CONCLUSIONS: On-demand use of rabeprazole for the management of symptomatic GERD incurs the least cost in comparison to the other PPIs evaluated. Utility gains were comparable for all on-demand PPIs.