Objective To compare the difference in efficacy of early precut of pancreatic duct sphincter and pancreatic duct stent placement in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) during high-risk patients. Methods A prospective study was conducted on 61 eligible patients who underwent ERCP treatment in Department of Hepatobiliary Surgery of The First Affiliated Hospital of Xi’an Jiaotong University and Xianyang Hospital of Yan’an University, from November 2016 to November 2017. All cases were randomly divided into early pancreatic sphincterotomy group (n=30) and pancreatic duct stenting group (n=31) . The success rate of intubation, intubation, and incidence of complication were compared. Results There was no significant difference in the success rate of the first intubation between the 2 groups (P=0.580), but the intubation time of the early pancreatic sphincterotomy group was shorter than that of the pancreatic duct stenting group (P=0.007). In the early pancreatic sphincterotomy group, there was 1 case of post-ERCP pancreatitis, 1 case of biliary tract infection, and 1 case of postoperative bleeding. In the pancreatic duct stenting group, there was 1 case of post-ERCP pancreatitis, and 2 cases of biliary tract infection. No severe complications such as perforation or severe acute pancreatitis occurred in both 2 groups. There was no significant difference in the incidence of total complications and specified complication (included post-ERCP pancreatitis, biliary tract infection, and postoperative bleeding) between the 2 groups (P>0.05). Conclusions Thereis no significant difference in the incidence of postoperative pancreatitis after early precut of pancreatic duct sphincter and pancreatic duct stenting placement in patients with high-risk, but intubation time of early precut of pancreatic duct sphincter method is shorter than the pancreatic duct stenting placement method.