Objective To assess the efficacy of triple therapy including proton pump inhibitor (PPI), levofloxacin and amoxicillin for the first-line treatment of H. pylori infection, and the relation between H. pylori eradication and CYP2C19 genetic polymorphism. Methods Two hundred and five H. pylori-positive patients were divided into group E_(20) (esomeprazole 20 mg twice daily), group E_(40)(esomeprazote 40 mg twice daily),group R (rabeprazole 10 mg twice daily) and group L (lansoprazole 30 mg twice daily). Besides PPI, all patients were received levofloxacin 500 mg daily and amoxicillin 1000 mg twice daily for 1 week. The CYP2C19 genotypes were detected in 161 patients. The eradication of H. pylori were analyzed by intention-to-treat (ITT) and per protocol (PP) methods.Results The H. pylori eradication was 86.70% in group E_(20), 88.5% in group E_(40),73.5% in group R and 78.1% in group L. Whereas the H. pylori eradication was 90% in patients with PM genotype,81.5% in patients with HetEM genotype and 82.1% in patients with HomEM genotype. The H.pylori eradication was 83.4% and 79.00% by per protocol (PP) and intention-to-treat (ITT) analyses,respectively. There was no significant difference in H. pylori eradication among four groups (P>0.05), and no relation was found between H. pylori eradication and genotypes (P>0.05). Conclusions PPI based triple therapy was effective in eradication of H. pylori, which is not influenced by CYP2C19 genotypes.