BACKGROUND: This study aimed to investigate the efficacy of bismuth added to a 2-week triple therapy consisting of tegoprazan (TPZ), amoxicillin, and clarithromycin for first-line eradication. RESEARCH DESIGN AND METHODS: We reviewed the retrospective data of patients who received a 2-week TPZ-based triple therapy with or without 300 mg bismuth twice daily. The primary endpoint was the eradication rate of adding bismuth to the TPZ-based triple regimen (TAC-B group), compared to no bismuth added (TAC group). RESULTS: In total, 306 and 256 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. The eradication success rates were significantly higher in the TAC-B group than in the TAC group (ITT, 82.9% vs. 71.8%,  = 0.029; PP, 95.8% vs. 87.5%,  = 0.027, respectively). The adherence rate to the eradication regimen was 100% in the TAC-B group and 97.0% in the TAC group. The adverse drug event rate in the TAC-B group was comparable to that in the TAC group (29.2% vs. 27.3%,  = 0.742). No use of bismuth was significantly associated with eradication failure ( = 0.038). CONCLUSIONS: The bismuth add-on increased the first-line eradication rate of 2-week TPZ-based triple therapy. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05453994.