Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.