Objective To compare the efficacy of different doseesomeprazole-based triplen therapies for Helicobacter pylori (Hp)eradication. Methods Two hundred and forty Hp-infected patients were randomly assigned to undergo high-dose (40 mg) or low-dose (20 mg) esomeprasole combined with clarithromycin (500 mg) and amoxicillin (1g) twice a day for one week. Hp eradication test was performed at 4 weeks after the end of treatment to evaluate the response to therapy. Results One hundred and fourteen patients were followed up in high-dosepatients, and 104 were Hp eradication. One hundred and thirteen patients were followed up in low-dosepatients, and 101 were Hp eradication. There was no significant difference in eradication rate of intention-to treat analysis and per protocol analysis between high-dose and low-dosepatients [86.7%(104/120) vs 84.2% (101/120) and 91.2% (104/114) vs 89.4% (101/113), P>0.05]. There was no significant difference in the rate of adverse effect between high-dose and low-dosepatients (8.3%(10/120)vs 6.7%(8/120), P>0.05). Conclusion It demonstrates that low-doseesomeprazole-based triple therapy has a similar Hp eradication rate compared with high-doseesomeprazole-based therapy in China.