Abstract: OBJECTIVE To conduct a Meta-analysis of study comparing esomeprazole with first-generation pump inhibitors in the treatment of Helicobacter pylori infection. METHODS Retrieved from Clinical Controlled Trials Database of Cochrane Library, PubMed, EMBase, Wanfang Database, CNKI, VIP and CBM, randomized controlled trials were screened according to predefined inclusion and exclusion criteria. Then the quality of the included studies was evaluated and Meta-analyses was performed by RevMan 5.1 software. RESULTS A total of 15 articles involving 3 032 patients were included. All these articles were regarded as high quality according to Jadad evaluation criteria. The result of meta-analysis showed that the risk ratio was significantly different when esomeprazole compared with first-generation pump inhibitors WMD=1.32, 95％CI(1.09, 1.59), P=0.004. There were no significant differences in the risk ratio between two groups when the dosage of esomeprazole was 20 mg bid WMD=1.17, 95％CI(0.93, 1.48), P=0.18. But the risk ratio was significantly different when the dosage of esomeprazole was 40 mg bid WMD=2.27, 95％CI(1.07, 4.82), P=0.03. In PM patients, no differences were found between esomeprazole and first-generation PPIs WMD=1.19, 95％CI(0.22, 6.53), P=0.84. In EM patients, however, the eradication rates in esomeprazole group were significantly better than first-generation PPIs groupWMD=1.84, 95％CI(1.13, 2.98), P=0.01. CONCLUSION Esomeprazole shows better overall H. pylori eradication rates than first-generation pump inhibitors. This clinical benefit is more pronounced in esomeprazole 40 mg bid regimens. In EM patients, the eradication rates are significantly better with esomeprazole.