Background/Aim: Increasing resistance of Helicobacter pylori to antimicrobials necessitated the development of new regimens and the modification of existing regimens. The present study aimed to compare the efficacy of two bismuth-containing quadruple regimens-one including clarithromycin (C) instead of metronidazole (M) and triple therapy. Patients and Methods: Patients with H. pylori infection given the following regimens were sequentially enrolled in this retrospective study: (1) Triple therapy: Lansoprazole 30 mg b. i. d., clarithromycin 500 mg b. i. d., and amoxicillin 1 g b. i. d., (2) bismuth group C: Lansoprazole 30 mg b. i. d., clarithromycin 500 mg b. i. d., amoxicillin 1 g b. i. d., and bismuth subsalicylate 524 mg b. i. d., and (3) bismuth group M: Lansoprazole 30 mg b. i. d., amoxicillin 1 g b. i. d., metronidazole 500 mg t. i. d., and bismuth subsalicylate 524 mg b. i. d. for 14 days. Gastroscopy and C-14-urea breath test were performed before enrollment, and urea breath test was repeated four weeks after the treatment. Results: At per-protocol analysis, the eradication rates were 64.7% (95% confidence interval 60.4-68.7) with the triple therapy (n = 504), 95.4% (95% confidence interval 91.5-99.4) with the bismuth group C (n = 501), and 93.9% (95% confidence interval 89.7-98.7) with the bismuth group M (n = 505). The eradication rates were similar between the two bismuth groups (P > 0.05) but significantly greater than that of the triple therapy (P < 0.05). Conclusion: In our study, both of the bismuth-containing quadruple therapies reached high eradication rates, whereas triple therapy was shown to be ineffective. Moreover, clarithromycin may also be a component of bismuth-containing quadruple therapy.