OBJECTIVES: The aim of the study was to compare the cost-effectiveness of esomeprazole with other PPIs currently reimbursed in Poland in the acute treatment of gastroesophageal reflux disease (GERD). METHODS: A decision analysis model simulating the treatment of GERD over the course of 8 weeks was developed. The duration of treatment is in line with the one recommended by the general guidelines. Healing rates were pooled from the existing clinical trials comparing esomeprazole with other PPIs. All patients were initially treated with PPI at high-dose for 4 weeks. Subsequently, healing was verified by the gastroenterologist and upper gastrointestinal endoscopy. Patients with treatment success at 4 weeks started maintenance treatment with a low-dose PPI and were assumed to remain healed for the duration of the model. Patients unhealed at 4 weeks were prescribed a further 4-week treatment course with the same high-dose of PPI, followed by a second visit with endoscopy was carried out. The analysis was conducted from a public payer perspective.  Cost of PPIs was derived from the publicly available Ministry of Health (MoH) price list. Gastroenterologist visit and endoscopy were estimated on the basis of National Health Fund (NHF) data. Data are presented in EUR (1 EUR = 4.00 PLN). RESULTS: Over the course of 8 weeks, treatment with esomeprazole was projected to have slightly better net clinical benefits over treatment with lansoprazole, omeprazole or pantoprazole (the QALY gains were 0.0002, 0.0003 and 0.0003, respectively). There were also marginal cost savings achieved by esomeprazole (1.23 EUR versus lansoprazole, 2.27 EUR versus omeprazole and 1.51 EUR versus pantoprazole), therefore esomeprazole was projected to have a dominant position versus other PPIs in the cost-effectiveness analysis. CONCLUSIONS: Esomeprazole provides greater effectiveness at a lower cost compared with other PPIs currently reimbursed in Poland in the treatment of GERD.