The Helicobacter pylori (H. pylori) eradication rate has decreased slightly because of the increasing number of clarithromycin-resistant bacteria. However, vonoprazan-based triple therapy (vonoprazan 40 mg/day+amoxicillin 1,500 mg/day+clarithromycin 800 mg/day) retains the potential to eradicate H. pylori better than other proton pump inhibitor (PPI) -based triple therapies. Vonoprazan is a potassium-competitive acid blocker that differs from PPIs in its mechanism of action. We compared vonoprazan-based triple therapy and esomeprazole-based triple therapy (esomeprazole 40 mg/day+amoxicillin 1,500 mg/day+clarithromycin 800 mg/day) in terms of the H. pylori eradication rate. Vonoprazan-based triple therapy was used to treat patients with a history of H. pylori-infected gastritis and gastric or duodenal ulcers caused by H. pylori during the period April 2015 to April 2016, and the eradication rates were compared with those obtained in similar patients treated with esomeprazole-based triple therapy between August 2014 and March 2015. The first-line H. pylori eradication rate of vonoprazan-based triple therapy was 92%, and the second-line eradication rate was 100%. The corresponding figures for esomeprazole-based triple therapy were 84.8% and 60%. Subgroup analyses of the first-line H. pylori eradication rate showed almost the same trends. There was no statistically significant difference between the H. pylori eradication rate of vonoprazan-based triple therapy and the eradication rate of esomeprazole-based triple therapy.