Objective: To compare the clinical efficacy of modified pancreaticojejunostomy versus conventional pancreaticojejunostomy in pancreaticoduodenectomy. Methods: Using a retrospective historical approach, the clinical data of 79 patients with periampullary tumors undergoing conventional pancreaticojejunostomy for digestive tract reconstruction (conventional pancreaticojejunostomy group) from Jan 2014 to Nov 2015, and 87 patients with periampullary tumors undergoing modified pancreaticojejunostomy for digestive tract reconstruction (modified pancreaticojejunostomy group) from Dec 2015 to Dec 2017, were analyzed. The conventional pancreaticojejunostomy was end-to-side anastomosis between the remnant pancreas and lateral jejunal wall, and the modified pancreaticojejunostomy was mucosa-to-mucosa anastomosis between the remnant pancreas and lateral jejunal wall. The main clinical variables between the two groups were compared. Results: There were no significant differences in general data, surgical procedures, overall operative time, and intraoperative blood loss between the two groups (all P>0.05). Despite the similar overall operative times between the two groups, the time for pancreaticojejunostomy in modified pancreaticojejunostomy group was two times of that in conventional pancreaticojejunostomy group. The incidence of grade A or B pancreatic fistula in the modified pancreaticojejunostomy group was significantly lower than that in conventional pancreaticojejunostomy group (P=0.027 and 0.019), and the incidence of biliary fistula or abdominal infection was also significantly lower than that in conventional pancreaticojejunostomy group (P=0.014 and 0.011). The incidence of grade C pancreatic fistula, intestinal fistula, intra-abdominal bleeding, and delayed gastric emptying showed no statistical differences between the two groups (all P>0.05). Conclusion: Compared with the conventional pancreaticojejunostomy, the modified pancreaticojejunostomy offers reduced incidence of grade A and B pancreatic fistula, biliary fistula and abdominal infection. Although this modified procedure has somewhat prolonged operative time, it is recommended to be further used in clinical practice.