OBJECTIVES: To compare the efficacy of esomeprazole with that of the European licensed standard doses of PPIs for the relief of GORD-associated symptoms in patients with reflux oesophagitis (i.e. esomeprazole 40 mg once-daily compared with lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, or rabeprazole 20 mg once-daily). METHODS: A systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomised controlled trials (RCTs) in patients with erosive oesophagitis was conducted in January 2007. Data on relief of GORD symptoms at 4 weeks were extracted and re-analysed if not analysed by intention-to-treat. The summary effect estimate (relative risk [RR]) was calculated by meta-analysis using a fixed-effects model. Publication bias was assessed using funnel plots. RESULTS: Of 347 papers identified in the literature search, 11 were found to be head-to-head comparisons of a standard dose of PPI and esomeprazole 40 mg. Five RCTs were excluded as they did not contain any extractable data on the required outcomes at 4 weeks. The remaining 6 RCTs were all randomised, double-blind, double-dummy, had appropriate patient follow-up, and were of sufficient quality to be included. A meta-analysis of complete resolution of heartburn showed that significantly more patients were heartburn-free with esomeprazole versus other standard-dose PPIs (RR 1.08; 95% CI: 1.06 to 1.11; p<0.00001). Heartburn resolution was consistent across all degrees of initial severity (mild, moderate, severe). There were no significant differences in treatment effect for dysphagia and epigastric pain, but significantly fewer patients had acid regurgitation with esomeprazole versus other standard-dose PPIs (RR 1.03; 95% CI: 1.01 to 1.05; p=0.002). Publication bias did not appear to affect the results significantly. CONCLUSION: Esomeprazole significantly improves symptoms of heartburn and acid regurgitation when compared with other standard-dose PPIs in patients with reflux oesophagitis.