Background: Postoperative pancreatic fistula (POPF) is the leading determinant of morbidity and mortality and reaches up to 49.9% of patients underwent pancreaticoenteric anastomosis during pancreaticoduodenectomy (PD). This study was to evaluate the feasibility of pancreaticoenteric anastomosis during pancreaticoduodenectomy (PD), and to evaluate the strategies of reducing the incidence of postoperative pancreatic fistula. Methods: This prospective study included 119 patients who underwent PD for resectable tumors. The patients were divided into two groups according to the diameter of the pancreatic duct: those with a dilated (≥3 mm) and those with small (<3 mm) pancreatic duct. Hong's type III binding pancreatogastrostomy (HBPG) was performed in 56 patients with a small duct, and pancreatic duct-to-jejunal mucosa (DM) anastomosis was performed in 63 patients with a dilated duct. Results: The pancreatic duct diameter was significantly smaller in the HBPG than in DM anastomosis group (2.26 ± 0.53 mm vs. 5.03 ± 1.76 mm, P < 0.05). The overall incidence of postoperative pancreatic fistula was 11.8%; fistulas affected 6 of 56 (10.7%) patients in the HBPG group (Grade A, n = 4; Grade B, n = 2) and 8 of 63 (12.7%) patients in the DM anastomosis group (Grade A, n = 6; Grade B, n = 2). The overall complication rate was 37.0%; complications affected 24 of 56 (42.9%) patients in the HBPG group and 20 of 63 (31.7%) patients in the DM anastomosis group. Grade >IIIa complications occurred in 8 (14.3%) and 6 (9.5%) patients in the HBPG and DM anastomosis groups, respectively. The average postoperative hospital stay was 15.39 ± 6.88 days in the HBPG group and 13.24 ± 4.72 days in the DM anastomosis group. There were no significant differences in the frequency of complications such as postoperative bleeding, biliary fistula, delayed gastric emptying, gastrointestinal anastomotic fistula, reoperation rate, or readmission rate between the two groups. Conclusions: The individual strategy based on the pancreatic duct diameter might effectively reduce the incidence of postoperative pancreatic fistula and other severe complications of PD. HBPG anastomosis is suitable for patients with pancreatic duct smaller than 3 mm. The size of the pancreatic duct is also one of the considerations for the selection of pancreatic and enteric duct anastomosis. © 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China