OBJECTIVES: To compare the cost-effectiveness of therapy of different forms of GERD with esomeprazole and other proton pump inhibitors (PPIs) in Poland. METHODS: Results of clinical trials with esomeprazole in comparison with equivalent doses of other PPIs in the treatment of erosive esophagitis (EE - 6 RCTs), non-erosive reflux disease (NERD – 1 RCT) and GERD maintenance therapy (2 RCTs) were systematically reviewed. Meta-analysis was conducted as appropriate, relative risk values were calculated. Cost data derived from Polish Ministry of Health and pharmacies in Wroclaw. Cost effectiveness ratios and incremental cost effectiveness ratios were assessed for 100 patients. RESULTS: In the treatment of EE esomeprazole was significantly more effective than other PPIs. For 4 weeks therapy ICER values (esomeprazole 40 mg vs. omeprazole 20 mg and pantoprazole 40 mg) were 614 PLN and 906.33 PLN respectively if original and generic esomeprazole products were taken into account and  118.22 PLN and 162.67 for generics. For 8 weeks therapy ICER values  (esomeprazole 40 mg vs. omeprazole 20 mg, lansoprazole 30 mg and pantoprazole 40 mg) were: 430.45 PLN,  329.47 PLN and 325.33 PLN (for generics and original esomeprazole) and 1869.58 PLN, 2677.89 PLN  and 1812.67, respectively for generics. Differences in effectiveness of NERD therapy with esomeprazole and other PPIs were not statistically significant. The replacement of pantoprazole 20 mg with more effective esomeprazole 20 mg in the 6-month maintenance therapy was associated with a marginal cost  of 3078.01 PLN (only generics included) and 4590.91 PLN (for original esomeprazole and generics) respectively. CONCLUSIONS: 1) For  4 and 8 weeks therapy of EE esomeprazole has to be recognized as a cost-effective option. 2) In the NERD treatment the choice of PPI should be based on the price of medicament. 3) The use of esomeprazole in GERD maintenance therapy is associated with a very high ICER.