The maximal effect of proton pump inhibitors (PPI) is reported to take 5 days. However, most current protocols start PPI on the day of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the benefit of 5 days pretreatment with oral PPI before ESD to prevent bleeding. This was a prospective randomized controlled trial. Patients were administered oral rabeprazole 20 mg or placebo twice daily for 5 days before ESD. Intravenous pantoprazole 40 mg was administered 2 h before ESD and at postprocedure day 1, and then oral rabeprazole 20 mg was administered once daily. Follow-up endoscopy was performed on days 1 and 30. Forty-eight-hour measurement of intragastric pH was performed in 26 patients. The primary endpoint was major bleeding related to ESD. One-hundred and twenty patients were enrolled. Of these, 45 in the pretreatment and 53 in the placebo group were analyzed. Each group had three cases of major bleeding. There were no significant differences in the ulcer healing rate. Intragastric pH percentage times greater than 4, 5, and 6 were 86.61 +/- A 19.45 %, 83.30 +/- A 22.06 %, and 76.86 +/- A 25.35 %, respectively, in the pretreatment and 85.54 +/- A 19.45 %, 84.08 +/- A 27.11 %, and 81.53 +/- A 27.81 %, respectively, in the placebo group, without significant differences. Preprocedural administration of rabeprazole offers no additional benefit over postprocedural administration alone in preventing major bleeding after gastric ESD.