It remains challenging for endoscopists to manage pancreaticobiliary diseases in patients with ectopic papilla of Vater by endoscopic retrograde cholangiopancreatography (ERCP). The present study sought to evaluate the efficacy and safety of ERCP for this issue.Consecutive patients with ectopic papilla of Vater who underwent initial ERCP due to pancreaticobiliary diseases were retrospectively analyzed.One hundred seven patients with ectopic papilla of Vater were included. The success rate of cannulation was 83.2%. Endoscopic sphincterotomy, endoscopic papillary balloon dilation, and mechanical lithotripsy were performed in 12 (11.2%), 25 (23.4%), and 1 (0.9%) patients, respectively. The technical success rate was 83.2%; of these, endoscopic nasobiliary drainage, endoscopic retrograde biliary drainage, endoscopic retrograde pancreatic drainage, and stone extraction was conducted in 61 (57.0%), 17 (15.9%), 5 (4.7%), and 45 (42.1%) patients, respectively. Bile duct stone size ≥1 cm, number ≥2, and duodenum stenosis were risk factors for stone extraction inability. Adverse events occurred in 20 (18.7%) patients, including post-ERCP pancreatitis (3.7%), hyperamylasemia (12.1%), and infection of biliary tract (2.8%); all of the adverse events were mild and alleviated by conventional therapies.ERCP is an appropriate choice for pancreaticobiliary diseases in patients with ectopic papilla of Vater due to its high efficacy and safety. Bile duct stone size ≥1 cm, number ≥2, and duodenum stenosis increase difficulties for stone extraction.