Objective: To investigate clinical manifestations, risk factors, diagnosis and treatment of pancreatico-enteric anastomotic stenosis after pancreaticoduodenectomy (PD). Methods: The clinical data of patients developing pancreatico-enteric anastomotic stenosis after PD treated from January 2008 to January 2018 were reviewed. The diagnosis and treatment process and follow-up results of the patients were analyzed and summarized. Results: Six patients developing pancreatico-enteric anastomotic stenosis after PD were enrolled, of whom, the primary disease in one case was serous cystadenoma, two cases was duodenal papillary carcinoma, two patients was chronic pancreatitis and one case was ampullary carcinoma; 5 cases underwent pancreaticojejunostomy and one case underwent pancreaticogastrostomy; perioperative complications occurred in 3 cases, including biochemical leak, grade B pancreatic fistula and delayed gastric emptying in one case each. The main manifestation of the 6 patients was repeated onset of acute pancreatitis with no obvious predisposing cause after PD, and their pancreatico-enteric anastomotic stenosis were diagnosed by MRCP and/or CT. The median time from PD to diagnosis was 54 (15–84) months. After diagnosis, 5 patients underwent reconstruction of the pancreatico-enteric anastomosis, of whom, no special discomforts were noted in 2 cases within 6- and 8-month follow-up period respectively, and acute pancreatitis recurrence occurred and with repeated onset in the remaining 3 cases during follow-up from 6 to 39 months; one patient refused further surgery and subsequently still suffered from repeated onset of acute pancreatitis. Conclusion: Pancreatico-enteric anastomotic stenosis is one of the rare complications after PD. The stenosis frequently occurs in the pancreatic duct opening. Its potential risk factors include chronic pancreatitis, postoperative pancreatic fistula, intra-abdominal infection and pancreaticogastrostomy. Its main manifestation is repeated onset of acute pancreatitis. Reconstruction of the pancreatico-enteric anastomosis is a commonly used and safe treatment method, but the recurrence rate of pancreatitis after surgery is still high.