Objective: To evaluate the practicability, safety and effectiveness of pancreatic-duct hanging and end-to-side continuous pancreaticojejunostomy in pancreaticoduodenectomy (PD). Methods: Using a prospective, randomized, controlled design, 165 patients undergoing PD were allocated to use an end-to-end or end-to-side invagination anastomosis (group A), end-to-side mucosa-to-mucosa anastomosis (group B) or pancreatic-duct hanging and end-to-side continuous pancreaticojejunostomy (group C) for pancreaticojejunostomy, respectively. The rate of pancreatic fistula and other complications after PD among the groups were compared. Results: The overall incidence of pancreatic fistula was 13.9% (23/165). The incidence of pancreatic fistula in group A, B and C was 23.1% (12/52), 18.8% (9/48) and 3.1% (2/65) respectively, and it was significantly lower in group C than that in group A and B (both P<0.05). In addition, the operative time, intraoperative blood loss and postoperative plasma tube drainage volume were significantly less than those of group A and B (all P<0.05), while no significant difference was noted with regard to other complications among the three groups (all P>0.05). There were no significant differences between group A and B in all recorded variables (all P>0.05). Conclusion: Pancreatic-duct hanging and end-to-side continuous pancreaticojejunostomy can reduce the incidence of pancreatic fistula after PD. Furthermore, it is safe and applicable, so it deserves to be widely used.