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[Background and aims]The urine trypsinogen-2 has been used successfully in the diagnosis of pancreatitis of various etiologies, but has been rarely studied in postoperative pancreatitis following pancreatic surgery. The aim of this study was to reveal the risk factors for the postoperative acute pancreatitis after pancreaticoduodenectomy, and also to analyze the possible association of postoperative acute pancreatitis and postoperative pancreatic fistula.[Methods]131 patients undergoing pancreaticoduodenectomy who measured postoperative urine trypsinogen-2 were included in this study: 56 females and 75 males (median age 68 years; range 19-88). The pancreatic anastomosis was reconstructed with a two-layered duct-to-mucosa pancreaticogastrostomy with internal stent into the posterior wall of the stomach. The concentration of trypsinogen-2 in the urine samples on the postoperative day 3 was measured by a quantitative immunofluorometric assay. Postoperative acute pancreatitis was defined chemically as the elevation of urine trypsinogen-2 levels more than 50 µg/l. Levels of drain amylase was also measured daily, and postoperative pancreatic fistula was classified into three categories by International Study Group Pancreatic Fistula (ISGPF) criteria. We analyzed the risk factors of postoperative acute pancreatitis by logistic regression analysis, and also analyze the association of postoperative acute pancreatitis and postoperative pancreatic fistula. [Results]The incidence of postoperative acute pancreatitis was 35/131 (27%). Univariate analysis revealed that the soft pancreatic parenchyma, non pancreatic adenocarcinoma, main pancreatic duct diameter less than 3mm, and preoperative biliary drainage were significant risk factors for the development of postoperative acute pancreatitis. Multivariate analysis demonstrated that the independent risk factor for postoperative acute pancreatitis is soft pancreatic parenchyma. The rate of ISGPF was 18 of 131 patients (14%). Of these, 14 patients (11%) had grade A, three patients (2%) had grade B, and one patient (1%) had grade C by ISGPF criteria. Postoperative acute pancreatitis was significantly associated with postoperative pancreatic fistula (ISGPF grade A+B+C, p< 0.01) and it was also associated with clinically relevant pancreatic fistula (ISGPF grade B+C, p<0.05). [Conclusion]Soft pancreatic parenchyma is an independent risk factor for postoperative acute pancreatitis defined by urine trypsinogen-2 levels. Postoperative acute pancreatitis might play an important role in the pathogenesis of postoperative pancreatic fistula following pancreaticoduodenectomy.