BACKGROUND: Endoscopic submucosal dissection (ESD) is a technically difficult and time-consuming procedure. We aimed to investigate the efficacy and safety of ESD using a multibending endoscope to treat superficial gastrointestinal neoplasms. METHODS: Patients with a single early gastric cancer who met the absolute or expanded indications for ESD according to the Japanese gastric cancer treatment guidelines were enrolled and randomly assigned to undergo ESD using a conventional endoscope (C-ESD) or a multibending endoscope (M-ESD). Randomization was stratified by ESD operator experience and tumor location. The primary outcome was ESD procedure time, calculated as the time from the start of submucosal injection to complete removal of the tumor. RESULTS: 60 patients were analyzed (30 C-ESD, 30 M-ESD). The mean (standard deviation [SD]) ESD procedure times for M-ESD and C-ESD were 34.6 (SD 17.2) and 47.2 (SD 26.7) minutes, respectively (P = 0.03). Muscle layer damage occurred significantly less frequently with M-ESD (0.2 [SD 0.7] vs. 0.7 [SD 1.0]; P = 0.04). There were no significant differences between the two techniques in procedure time or damage to muscle layers for tumors located in the lower third of the stomach. CONCLUSIONS: ESD procedure time was significantly shorter with the multibending endoscope and fewer muscles were damaged. We recommend multibending endoscopy for ESD in the upper and middle thirds of the stomach to reduce procedure time and incidence of complications.