Abstract: Objective To investigate the effect of esomeprazole- and omeprazole-based triple therapy regimens in the treatment of duodenal ulcer with Helicobacter pylori (Hp) infection. Methods Totally 104 patients with duodenal ulcer and Hp infection were randomly divided into group A (52 cases) treated with esomeprazole (20 mg), amoxicillin (1 000 mg) and clarithromycin (500 mg) twice daily and group B (52 cases) treated with omeprazole (20 mg), amoxicillin (1000 mg) and clarithromycin (500 mg) twice daily. The treatment lasted for 7 days, after which abdominal pain relief rate, ulcer healing rate and eradication rate of Hp as well as adverse effects of the medication were evaluated and compared. Results On the first and second days of medication, the abdominal pain relief rates were 34.6% and 59.6 % respectively in group A, significantly higher than those in group B (17.3% and 38.5%, respectively, P<0.05). Ulcer healing rate and Hp eradication rate were 92.3% and 88.5 % in group A, and 88.5% and 82.7% in group B, showing no significant differences between the two groups (P>0.05). The adverse effects of the medication were rare in both groups without significant differences. Conclusion Esomeprazole-based triple therapy may effectively eradicate Hp infection and promote duodenal ulcer healing with good tolerance, capable of achieving more speedy pain relief than omeprazole-based therapy.