OBJECTIVES: To compare the clinical and cost-effectiveness of esomeprazole and other PPI (omeprazole, lansoprazole, pantoprazole and rabeprazole) in patients with GERD. METHODS: The clinical effectiveness analysis according Cochrane Collaboration guidelines was performed. Cost-effectiveness decision model was performed from a payer's perspective, with a time horizon of 8 weeks. RESULTS: 8, 13, 6, and 3 RCT comparing esomeprazole to lansoprazole, omeprazole, pantoprazole and raboprazole were included. Esomeprazole 40 mg was significantly more effective compared to lansoprazole 30 mg and omeprazole 20 mg in healing reflux esophagitis after 4 and 8 weeks (OR=1.25 and 1.29 vs. lansoprazole; OR = 1.84 and 2.10 vs. omeprazole). Esomeprazole is also more effective than lansoprazole and omeprazole for variables evaluating reflux symptoms. Compared to pantoprazole 40 mg, esomeprazole 40 mg was statistically significantly more effective in terms of healing erosive oesophagitis after 4-6 and 8-10 weeks (OR=1.35 and 1.36, respectively), time to reach sustained heartburn resolution and proportion of heartburn-free days. Result of a single trial showed that pantoprazole resulted in faster first-time relief from GERD-related symptoms than esomeprazole. Based on a single study comparing esomeprazole 20 mg and rabeprazole 10 mg in patients with non-erosive GERD, both treatments had similar efficacy in relief of symptoms. Triple therapy regimens with either esomeprazole or omeprazole were similarly effective in eradicating Helicobacter pylori. The safety analysis showed no significant differences in the frequency of adverse events between esompeprazole and other PPI except for headaches, which occurred more frequently in the desloratadine group than in the lansoprazole group. The ICER for esomeprazole per additional patient healed after 8 weeks was 7 858 PLN (vs lansoprazole), 2608 PLN (vs lansoprazole) and 6274 PLN (vs. pantoprazole). CONCLUSIONS: Esomeprazole is at least as effective as other PPI in the treatment of GERD.