Abstract: Objective To investigate the application and value of pancreatic stents combing nasal biliary tube (NBT) after Endoscopic Retrograde Cholangiopancreatography (ERCP) for removal of difficult and large common bile duct stones and its prevention of pancreatitis and hyperamylasemia. Methods From January 2016 to April 2018 a total of 113 patients who had difficult and large common bile duct stones received ERCP procedure in endoscopy center of Zibo Central hospital. They were randomized to non-stent group (NS group), who receive nasal biliary tube (NBT) placement after ERCP procedure, and stent group (S group). Patients in the stent group were treated with pancreatic stent and NBT placement after the conventional ERCP procedure. The successful stone clearance rate, incidence of post-ERCP pancreatitis (PEP), pancreatitis severity rating, hyperamylasemia and scores of abdominal pain were analyzed using t test and χ² test. Results Of the 57 patients in NS group, 47 achieved successful stone clearance(82.46%), 10 cases PEP(17.54%), 2 severe PEP and 15 cases hyperamylasemia (26.32%). The score of abdominal pain was (4.33±1.09). There were 56 patients in S group, 45 cases (80.36%) achieved successful stone clearance, PEP and hyperamylasemia were 3 cases and 6 cases respectively (5.36%,10.71%), and no severe PEP was observed in S group.The score of abdominal pain was (3.56±1.37). There was no significant difference in the successful clearance rate and the incidence of severe PEP between the two groups (all P>0.05), while PEP, the hyperamylasemia and the scores of abdominal pain were lower in the S group (all P<0.05). Conclusion For patients with difficult and large common bile duct stones, placement of pancreatic duct stent with NBT after ERCP can reduce PEP, the hyperamylasemia and score of abdominal pain, but do not have significant influence on successful clearance rate and the incidence of severe PEP.