Objective: To analyze the risk factors for intra-abdominal or gastrointestinal bleeding after pancreaticoduodenectomy (PD). Methods: The clinical data of 132 patients undergoing PD for periampullary cancer in the first affiliated hospital of Xinjiang Medical University during May 2005 and May 2011 were retrospectively analyzed. Results: Twenty-seven (20.5%) of the 132 patients developed postoperative hemorrhage (intra-abdominal or gastrointestinal bleeding), among whom, intra-abdominal bleeding occurred in 12 cases (9.1%), gastrointestinal bleeding occurred in 6 cases (4.5%), and both intra-abdominal and gastrointestinal bleeding occurred in 9 cases (6.8%). Univariate analysis results indicated that the intraoperative blood loss, volume of intraoperative blood transfusion, intra-abdominal infection, pancreatic fistula, biliary fistula and leakage of the pancreaticointestinal anastomosis were significantly associated with post-PD bleeding (all P<0.05). Multivariate analysis results identified that the intraoperative blood loss greater than or equal to 500 mL (P<0.000, 95%CI=6.900–103.775), pancreatic fistula (P=0.003, 95%CI=2.319–55.717) and intra-abdominal infection (P=0.043, 95%CI=1.046–19.364) were independent risk factors for post-PD bleeding. Conclusion: Intraoperative blood loss greater than or equal to 500 mL, pancreatic fistula and intra-abdominal infection are independent risk factors of post-PD bleeding.