Objective: To investigate the postoperative complications of endoscopic retrograde cholangiopancreatography (ERCP) and the prevention and treatment strategies. Methods: The clinical data of patients undergoing ERCP in Xiangya Hospital of Central South University from December 2010 to May 2015 were retrospectively analyzed. Results: Among a total of 461 patients undergoing ERCP, successful operation was performed in 394 cases (85.5%), and the causes for operative failure were mainly due to duodenal papilla blockage and intestinal stricture resulting from tumors, ulcers or other factors, which prevented the passage of endoscope or guide wire. Of the 394 patients, complications occurred in 126 cases (27.3%), including post-ERCP pancreatitis (PEP) in 29 cases (6.3%), transitional hyperamylasemia in 47 cases (10.2%), biliary tract infection in 25 cases (5.4%), hemorrhage in 22 cases (4.7%), basket incarceration and breakage in one case (0.2%), and pancreatic duct stent obstruction in one case (0.2%); no perforation occurred in any of the cases; 4 cases (0.9%) died, mainly due to systemic infection initiated by acute cholangitis. The incidence of complications of diagnostic ERCP was lower than that of therapeutic ERCP (23.4% vs. 34.7%, P<0.05). Conclusion: PEP and biliary tract infections are common and significant complications after ERCP. Strict adherence to the indications of ERCP, improvement in surgical skill and appropriate administration of medication are effective methods for reducing the incidence of post-ERCP complications.