Objective: To investigate the risk factors for occurrence of pancreatic fistula (PF) after pancreaticoduodenectomy (PD), so as to provide reference for prevention of PF after PD in clinical practice. Methods: The clinical data of 122 patients undergoing PD in Cancer Hospital affiliated to Xinjiang Medical University from January 2010 to march 2014 were reviewed. Fourteen factors potentially affecting the occurrence of PF were determined by univariate and multivariate Logistic regression analysis. Results: The incidence of PF in the whole group was 13.9% (17/122). Univariate analysis showed that history of upper abdominal surgery (P=0.024), preoperative bilirubin level (P=0.003), intraoperative blood loss (P=0.023), postoperative hemoglobin level (P=0.021), postoperative albumin level (P=0.046), and pancreatic duct diameter (P=0.007) were significantly associated with PF after PD. Multivariate analysis results demonstrated that the history of abdominal surgery, pancreatic duct diameter less than 3 mm, and postoperative hemoglobin level less than 90 g/L were independent risk factors for the occurrence of PF after PD (OR=4.308, 5.052, 3.958, all P<0.05). Conclusion: For PD patients with history of upper abdominal surgery, or with pancreatic duct diameter less than 3 mm or postoperative hemoglobin level less than 90 g/L, appropriate measures should be taken to reduce the incidence of PF after PD.