Objective To explore the application value of transpancreatic precut sphincterotomy combined with pancreatic duct stent placement for difficult intubation of endoscopic retrograde cholangiopancreatography (ERCP). Methods A total of 169 patients with difficult papilla intubation who underwent ERCP treatment in the Third Affiliated Hospital of Naval Medical University from January 2017 to December 2019 were included. Double guide wire intubation was used in 137 cases and transpancreatic precut sphincterotomy combined with pancreatic duct stent placement was used in 32 cases. The success rate of intubation, intubation time and postoperative complications of the two groups were compared. Results The success rates of intubation in the double guide wire group and the transpancreatic precut sphincterotomy combined with pancreatic duct stent placement group were 98.54% (135/137) and 100.00% (32/32) (P>0.05); the mean intubation time of the two groups were 15.69±9.07 min and 17.06±5.79 min (P>0.05); the incidence of postoperative complications were 25.55% (35/137) and 9.38% (3/32) (P<0.05), among which incidences of pancreatitis were 5.8% (8/137) and 0 respectively. Conclusion During difficult ERCP papilla intubation, the transpancreatic precut sphincterotomy combined with pancreatic duct stent placement can yield higher safety and a similar success rate compared with the double-guide wire technique, which is worthy of clinical application.