BACKGROUND/AIMS: Trends in successful eradication of Helicobacter pylori using first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin, and clarithromycin, have been understudied. We evaluated H. pylori eradication rates at a single center over the last 10 years and identified risk factors related to eradication failure. METHODS: This study included 1,413 patients who were diagnosed with H. pylori infection and received 7 days of triple therapy between January 2003 and December 2012. We investigated H. pylori eradication rates retrospectively with respect to the year of therapy, as well as demographic and clinical factors. H. pylori eradication was confirmed by a (13)C-urea breath test or a rapid urease test at least 4 weeks after the completion of triple therapy. RESULTS: The overall H. pylori eradication rate was 84.9%. Annual eradication rates from 2003 to 2012 were 93.5%, 80.0%, 87.2%, 88.5%, 92.0%, 88.3%, 85.7%, 84.1%, 83.7%, and 78.8%, respectively, by per-protocol analysis. The eradication rate with first-line triple therapy decreased during the last 10 years (p = 0.015). Multivariate analysis showed that female gender (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.12 to 2.55) and smoking (OR, 1.61; 95% CI, 1.05 to 2.47) were associated with the failure of H. pylori eradication therapy. CONCLUSIONS: The efficacy of first-line triple therapy for H. pylori infection has decreased over the last 10 years, suggesting an increase in antibiotic-resistant H. pylori strains. Thus, other first-line therapies may be necessary for H. pylori eradication in the near future.