BACKGROUND: There is no consensus regarding the degree of healing of endoscopic submucosal dissection (ESD)-induced ulcers and the optimal duration of proton pump inhibitor (PPI) treatment. AIM: To evaluate the degree of healing and the factors associated with healing of ESD-induced ulcers after PPI therapy for 4 weeks. METHODS: Fifty-six patients who underwent complete ESD for adenoma or early gastric cancer were enrolled. All patients underwent follow-up endoscopy to evaluate the degree of ulcer healing after pantoprazole therapy (40 mg per day) for 4 weeks. We evaluated change in size of ESD-induced ulcers between baseline and 4 weeks, and correlated relevant factors with degree of healing of small and large ulcers. RESULTS: At follow-up, 28 (50%) patients had large ulcers (area > 10 mm(2)). Ulcer size at 4 weeks was closely correlated with initial ulcer size (P < 0.001) and abruptly increased when initial ulcer size was larger than 4 cm. Comorbidity, procedure time, and initial specimen size were significantly associated with healing rate, but multivariate analysis showed that initial ulcer size was the only significant parameter (P < 0.015). CONCLUSIONS: Healing degree of ESD-induced ulcers at 4 weeks is dependent on initial ulcer size, indicating that duration of treatment with PPI should be dependent on initial ulcer size.