Objective: To assess the application value of pancreaticojejunostomy (PJ) with duct-to-mucosa running-through suture in pancreatieoduodenectomy (PD). Methods: The clinical data of 61 patients undergoing PD from January 2013 to March 2015 were retrospectively analyzed. Of the patients, 34 cases underwent PJ using the duct-to-mucosa through-and-through suture (observational group) and 27 cases underwent the conventional invagination PJ (conventional group). The clinical variables between the two groups were compared. Results: The general data were comparable between the two groups of patients. In observational group compared with conventional group, the time of intraoperative PJ was decreased [(14.9±1.6) min vs. (22.6± 2.6) min, P<0.05], the incidence of postoperative pancreatic fistula was reduced (11.76% vs. 37.03%, P<0.05), and the length of postoperative hospital stay was shortened [(16.5±4.9) d vs. (19.5±5.4) d, P<0.05]. There was no significant difference in intraoperative blood loss, incidence of other complications and postoperative 1-year survival between the two groups (all P>0.05). Conclusion: PJ with duct-to-mucosa running-through suture can reduce the incidence of postoperative pancreatic fistula, and it is a relatively simple and effective PJ method, and is recommended to be used in clinical practice.