BackgroundEndoscopic papillectomy (EP) is less invasive than surgery but procedure‐related adverse events (AEs) still frequently occur. This study compared the benefits of EP using a new optimal endoCUT setting on the VIO (Erbe) electrosurgical unit (VIO‐EP) with those using the conventional electrosurgical unit setting (ICC‐EP, Erbe).MethodsThis multicenter, retrospective, comparative cohort study included 57 patients who underwent VIO‐EP and 91 who underwent ICC‐EP. The primary outcome was occurrence of EP‐related AEs. Secondary outcomes were pathological findings (the resection margins, the R0 resection, and residual lesions).ResultsPancreatitis tended to be less common in the VIO‐EP group (5.3% vs. 9.9%, p = .248). Evaluation of computed tomography images showed that pancreatitis was confined to the pancreatic head in 77.8% of cases in the ICC‐EP group and in 33.3% of those in the VIO‐EP group. After exclusion of cases of delayed bleeding, pancreatitis tended to be less common in the VIO‐EP group; this finding was not statistically significant (2.3% vs. 8.2%, p = .184). In pathological findings, residual lesions were significantly less common in the VIO‐EP group.ConclusionsThe risks of pancreatitis and residual lesions after EP may be lower when the VIO electrosurgical unit is used with the optimal setting.