BACKGROUND Postoperative pancreatitis is one of the most serious complications in endoscopic retrograde cholangiopancreatography (ERCP). To detect potential risk factors for post-ERCP hyperamylasemia and pancreatitis. MATERIAL AND METHODS We reviewed 1786 ERCP procedures in Zhongnan Hospital of Wuhan University from January 2015 to April 2018. Clinical data were extracted, and the complications after ERCP procedures were re-evaluated. Single- and multiple-variable analyses were conducted to detect the potential risk factors. RESULTS We found that 1786 procedures were applied on 1707 patients; 64 patients (3.58%) developed pancreatitis, while asymptomatic hyperamylasemia occurred in 263 cases (14.73%). In multivariate analysis, pancreatic deep wire pass (odds ratio [OR]: 2.280, 95% CI [confidence interval]: 1.129-4.605, P=0.022), endoscopic metal biliary endoprosthesis (OR: 2.399, 95% CI: 1.120-5.138, P=0.024), operation after liver transplantation (OR: 3.057, 95% CI: 1.110-8.422, P=0.031), and fistulotomy (OR: 3.148, 95% CI: 1.036-9.561, P=0.043) were identified as independent risk factors for post-ERCP pancreatitis. Pancreatic deep wire pass (OR: 1.678, 95% CI: 1.136-2.478, P=0.009), fistulotomy (OR: 2.553, 95% CI: 1.096-5.948, P=0.030), and younger age (OR: 0.990, 95% CI: 0.980-0.999, P=0.037) were identified as independent risk factors for hyperamylasemia. CONCLUSIONS To prevent post-ERCP pancreatitis, it is important to avoid high-risk procedures such as fistulotomy and pancreatic deep wire pass, especially in high-risk patients with liver transplantation. For patients with endoscopic metal biliary endoprosthesis, clinicians should pay more attention to the occurrence of post-ERCP pancreatitis.