Graham DY, et al. - Vonoprazan seemed to restore the effectiveness of the combination of amoxicillin, clarithromycin, and proton pump inhibitor (triple Helicobacter pylori therapy). However, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in no benefit from the second antibiotic among the majority (> 85% currently in Japan) of those receiving vonoprazan–amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin). This leads to unnecessary clarithromycin use of somewhere between 2800 and 5600 kg per one million H. pylori treatment courses every year in Japan. Via this manuscript, researchers sought to discuss use of the principles of antimicrobial stewardship to generate potassium‐competitive acid blocker‐containing H. pylori therapies that will reliably achieve high H. pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently required for curtailing the use of vonoprazan triple therapies while improving overall H. pylori cure rates.