Objective To investigate the application value of transpancreatic septotomy with pancreatic duct stent or guide wire in difficult endoscopic retrograde cholangiopancreatography( ERCP). Methods A total of 309 patients who underwent difficult ERCP in Medical Center for Digestive Diseases,The Second Affiliated Hospital of Nanjing Medical University from June 2012 to May 2014 were selected; 228 patients among them received placement of pancreatic duct guide wire / plastic stent or conventional precut papillotomy,and achieved successful bile duct cannulation; the other 81 patients received transpancreatic septotomy with placement of guide wire( guide wire group,37 patients)or pancreatic duct stent( stent group,44 patients). The success rate and incidence of complications were compared between these two methods for cannulation. Results Of the 81 patients who underwent transpancreatic septotomy,77 achieved successful bile duct cannulation,and the success rate did not differ significantly between the guide wire group and stent group( 91. 89%( 34 /37) vs 97. 73%( 43 /44); P >0. 05). Seventeen patients experienced complications,with 8 cases of acute pancreatitis,3 cases of hemorrhage,and 1 case of biliary tract infection in the guide wire group,and 3 cases of acute pancreatitis,1 case of hemorrhage,1 case of biliary tract infection in the stent group;compared with the guide wire group,the stent group had a significantly lower incidence of complications( 11. 36% vs 32. 43%; χ2= 3. 75,P < 0. 05) and a significantly lower incidence of acute pancreatitis( 6. 82% vs 21. 62%; χ2= 2. 25,P < 0. 05). Conclusion Transpancreatic septotomy can further improve the success rate of bile duct cannulation with ERCP. The stent group has a higher success rate and a lower incidence of pancreatitis after ERCP than the guide wire group,and thus the application of stent is safer in clinical practice.