Aliment Pharmacol Ther 2011; 34: 1098–1105 Summary Background  The eradication rates of Helicobacter pylori (H. pylori) using a proton pump inhibitor (PPI)‐based triple therapy have declined due to antibiotic resistance worldwide. Aim  To compare the eradication rate of the 10‐day sequential therapy for H. pylori infection with that of the 14‐day standard PPI‐based triple therapy. Methods  This was a prospective, randomised, controlled study. A total of 409 patients with H. pylori infection were randomly assigned to receive either the 10‐day sequential therapy regimen, which consisted of pantoprazole (40 mg) plus amoxicillin (1000 mg) twice a day for 5 days, then pantoprazole (40 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice a day for another five consecutive days or the 14‐day PPI‐based triple therapy regimen, which consisted of pantoprazole (40 mg) with amoxicillin (1000 mg) and clarithromycin (500 mg) twice a day for 14 days. The pre‐ and post‐treatment H. pylori status were assessed by rapid urease test, urea breath test, or histology. Successful eradication was confirmed at least 4 weeks after finishing the treatment. Results  In the intention‐to‐treat analysis, the eradication rates of the 10‐day sequential therapy and of the 14‐day PPI‐based triple therapy were 85.9% (176/205) and 75.0% (153/205), respectively (P = 0.006). In the per‐protocol analysis, the eradication rates were 92.6% (175/205) and 85% (153/204), respectively (P = 0.019). There was no statistically significant difference between the two investigated groups regarding the occurrence of adverse event rates (18.9% vs. 13.3%, P = 0.143). Conclusion  The 10‐day sequential therapy achieved significantly higher eradication rates than the 14‐day standard PPI‐based triple therapy in Korea.