The goal of a new study published in Helicobacter aimed to validate the eradication rate of vonoprazan-based first-line triple therapy – combined with clarithromycin and amoxicillin, (V-AC) using clarithromycin (CAM)-susceptible testing. In this multicenter, prospective, randomized trial, 147 treatment-naïve H. pylori-positive patients were enrolled, of which 41 were with CAM-resistant infections and 106 had CAM-susceptible infections. The CAM-susceptible group patients were randomized to either the V-AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI-AC group (esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). The findings showed that all CAM-resistant H. pylori were eradicated by V-AC. On the other hand, the eradication rate of PPI-AC treatment in the CAM-susceptible H. pylori-infected patients was higher. Thus, it was inferred that PPI-AC is more efficacious for the treatment of CAM-susceptible H. pylori infection.