Objective:To explore the preventive effects of pancreatic duct stent combined with rectal administration of indomethacin suppository for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after difficult bile duct intubation during endoscopic retrograde cholangiopancreatography (ERCP).Methods:From January 2019 to December 2021, patients with biliary and pancreatic diseases undergoing ERCP in Hangzhou Hospital Affiliated to Nanjing Medical University were given 100 mg indomethacin suppository to anal canal 30 minutes before the operation. And those with difficult bile duct intubation during the operation ( n=204) were included in this study. According to the random number table, they were divided into the combination group (implanted with pancreatic duct stent during the operation, n=104) and the indomethacin group (not implanted with stent, n=100). The incidences of hyperamylasemia and PEP were compared between the two groups. Results:The incidences of postoperative hyperamylasemia [21.2% (22/104) VS 34.0% (34/100), χ2=4.22, P=0.040] and PEP [14.4% (15/104) VS 32.0% (32/100), χ2=8.88, P=0.003] in the combination group were significantly lower than those in the indomethacin group. There was no significant difference in the incidence of severe PEP between the two groups [1.0% (1/104) VS 1.0% (1/100), χ2=0.001, P=0.978]. Conclusion:Compared with rectal administration of indomethacin suppository alone, the incidences of hyperamylasemia and PEP after difficult bile duct intubation during ERCP can be further reduced when it is combined with pancreatic duct stent placement.