Objective To analyze cause and therapy of perforation of choledocho-pancreatico-duodenal junction associated with endoscopic retrograde cholangiopancreatography (ERCP) and its related procedures. Method The clinical data of 11 patients diagnosed with the perforation of choledocho-pancreatico-duodenal junction associated with the ERCP from January 2010 to January 2017 were analyzed retrospectively. Results Of 11 patients, 5 were diagnosed within 24 h, 3 were diagnosed between 24 h and 48 h, 3 were diagnosed above 48 h. Seven patients who immediately operated were cured following definitive diagnosis, 2 died after undergoing the delayed operation, 2 died after receiving the conservative treatment. The results of the anatomical-pathological factors showed that 4 were the anomalous arrangement of pancreaticobiliary ducts, 2 were the periampullary diverticula, 3 were the exposure of common bile duct in the pancreas level, 2 had no bile duct abnormality. Conclusions Preoperative evaluation on anatomical-pathological factor of bile duct is importance to effectively predict risk of perforation of choledocho-pancreatico-duodenal junction associated with ERCP. Early precise diagnosis and actively surgical operation are essential for optimal outcome in patient with perforation of choledocho-pancreatico-duodenal junction associated with ERCP.