Objective To investigate the application value of pancreatic duct guide wire and transpancreatic septotomy with precutting technique in difficult endoscopic retrograde cholangiopancreatography.Method258 patients who underwent difficult endoscopic retrograde cholangiopancreatography from April 2014 to April 2016 were selected as study subject, 128 patients among them received the technique of pancreatic duct guide wire, the other 130 patients received transpancreatic septotomy with precutting techniques. The success rate, intubation time and incidence of complications were compared between these two methods for cannulation.Result There was no signiifcant difference in preoperative clinical data between the two groups, the success rate did not differ signiifcantly between the two groups (93.75 % vs 93.85 %). Compared with transpancreatic septotomy with precutting techniques group, pancreatic duct guide wire group is less intubation time consuming (5.92 ± 0.69 vs 12.81 ± 3.67) min, the difference was statistically significant (t = -2.27,P < 0.05). 25 patients experienced complications, with 6 cases of acute pancreatitis, 2 cases of biliray tract infection in pancreatic duct guide wire group, and 8 cases of acute pancreatitis, 3 cases of hemorrhage,6 cases of biliray tract infection in transpancreatic septotomy with precutting techniques group. The pancreatic duct guide wire group had a signiifcantly lower incidence of complications (6.25 % vs 13.08 %). the difference was statistically signiifcant (χ2 = 3.27,P < 0.05). The incidence of acute pancreatitis did not differ signiifcantly between the two groups (4.69 % vs 6.15 %).ConclusionsPancreatic duct guide wire and transpancreatic septotomy with precutting techniques both can further improve the success rate of bile duct cannulation with ERCP. The incidence of acute pancreatitis did not differ significantly between two groups. But pancreatic duct guide wire group is less intubation time consuming, and had a significantly lower incidence of complications. Because of the convenience and safety of the pancreatic duct guide wire technique, and the insertion of the pancreatic duct does not increase the risk of postoperative acute pancreatitis. We think that this method is more worthy of Clinical promotion.