Objective To evaluate the efficacy of double U-stitch and modified “double U-stitch pancreaticojejunostomy” in pancreaticoduodenectomy. Methods We retrospectively analyzed the clinical information of 150 patients who underwent pancreaticoduodenectomy between January 2022 and September 2023 in Wang Wei’s team in department of pancreatic surgery, Fudan University Shanghai Cancer Center. The patients were divided into two groups according to the pancreaticojejunostomy method: the double U-stitch 1.0 group (70 cases before modification) and the double U-stitch 2.0 group (80 cases after modification). The postoperative complications of the two groups were compared. Results The overall postoperative complications were significantly lower in the double U-stitch 2.0 group as compared with the double U-stitch 1.0 group (13.8% vs. 38.6%, P=0.001). The incidence of clinically relevant pancreatic fistula was 18.6% in the double U-stitch 1.0 group, while this was significantly decreased in the double U-stitch 2.0 group (6.3%) (P=0.021). Postoperative extraluminal hemorrhage occurred in 5 patients in the double U-stitch 1.0 group, while in the double U-stitch 2.0 group, only one patient experienced postoperative intraluminal hemorrhage, the difference was statistically significant between two groups (P=0.007). The median postoperative length of hospital stay was significantly shorter in the double U-stitch 2.0 group than that in the double U-stitch 1.0 group (11 d vs. 14 d, P=0.001). Conclusions The modified “double U-stitch pancreaticojejunostomy” can significantly reduce the incidence of clinically relevant pancreatic fistula and other relevant severe complications, which helps improve the safety of the procedure.