Background Postoperative pancreatic fistula (POPF) represents the most important cause of morbidity after pancreaticoduodenectomy (PD) and contributes to prolonged hospitalization and increased mortality rates. This study presents a new technique, which involves end-to-end pancreaticojejunostomy with transpancreatic interlocking mattress sutures, and evaluates its safety and reliability. Methods From January 2011 to May 2012, 79 patients with periampullary malignancies underwent PD by using this modified technique, and the morbidity and mortality rates were calculated. Results In this study, all cases recovered well from PD. Four transpancreatic interlocking mattress sutures were performed in 79 patients. The median duration of surgery was 3.9hr (range 3.16.8), and the median time to perform pancreaticojejunostomy was 15.3min (range 924). Overall, morbidity occurred in 16 patients (22.3%), and the causes included upper gastrointestinal bleeding (n=2), biliary fistula (n=1), pulmonary infection (n=1), delayed gastric emptying (n=1), abdominal abscess (n=1, caused by PF), wound infection (n=3), arrhythmia or myocardial infarction (n=3), urinary tract infection (n=2), and POPF (n=2, 2.53%). One patient had grade A POPF, one had grade B POPF, and none of them had grade C POPF. No death occurred during surgery. Conclusion The end-to-end pancreaticojejunostomy with transpancreatic interlocking mattress sutures is a simple, rapid, safe, and reliable technique with low POPF rate and low delayed massive hemorrhage rate. J. Surg. Oncol. 2013 9999:XXXX. (c) 2013 Wiley Periodicals, Inc. J. Surg. Oncol. 2013;107:783788. (c) 2013 Wiley Periodicals, Inc.