<b><i>Background and Aims:</i></b> Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole. <b><i>Methods:</i></b> We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD. <b><i>Results:</i></b> Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; <i>p</i> = 0.07). However, for ulcers ≤35 mm, vonoprazan was superior to rabeprazole (42.2 vs. 19.2%; <i>p</i> &#x3c; 0.05). Reduction rates were superior for vonoprazan compared with rabeprazole (93.0 vs. 90.4%; <i>p</i> &#x3c; 0.05). In multivariate analysis, vonoprazan was superior to rabeprazole for ulcer scarring (OR 2.21; <i>p</i> &#x3c; 0.05), and ulcer location in the lower-third of the stomach had higher risk of incomplete scarring (OR 0.37; <i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> Vonoprazan was superior to rabeprazole for healing ESD-induced ulcers.