OBJECTIVE This study was aimed to assess whether the efficacy of one-week triple therapy comprising of proton pump inhibitor, amoxicillin and clarithromycin (PPI/A/C) on Helicobacter pylori (H. pylori) infection in Singapore has decreased over the duration from 2005 to 2010. METHODS The clinical data of H. pylori-positive patients treated with one-week PPI/A/C in 2005 and 2010 were reviewed retrospectively using a registry database. The primary endpoint was the difference in treatment success rate. RESULTS A total of 465 patients (n = 174 in 2005 and n = 291 in 2010) were analyzed. In 2010, compared with 2005, the mean age of patients was younger (47 vs 56 years, P < 0.001) and the proportion of foreigners was higher (19.9% vs 5.7%, P < 0.001). The success rate of H. pylori eradication remained similar over the two time periods (90.2% in 2005 vs 88.7% in 2010, P = 0.597). Multinomial logistic regression revealed that mean age, gender, diagnosis and nationality had no impact on the success of H. pylori eradication. CONCLUSIONS From 2005 to 2010, there was no significant decrease in the efficacy of one-week PPI/A/C for the treatment of H. pylori infection. This treatment regime remained an effective first-line therapy for H. pylori infection in Singapore.