Objective To explore the influencing factors of pancreatic fistula after pancreaticoduodenectomy (PD), and to compare the incidence of pancreatic fistula after pancreaticoduodenectomy with internal drainage of main pancreatic duct and external drainage according to the pancreatic fistula risk score (FRS) system, to provide the basis for the best drainage scheme in clinic. Methods The clinical data of 76 patients with PD who treated in the Affiliated Hospital of Xuzhou Medical University from January 2016 to December 2017 were analyzed retrospectively, to explore the risk factors of pancreatic fistula. Single factor analysis was based on group chi-square test or Fisher exact probability method, and multivariate analysis was based on unconditioned logistic regression model. According to the results of FRS, the difference of pancreatic fistula in different risk groups was explored. The statistical method was chi-square test. Results The incidence of pancreatic fistula after PD was 31. 5% in 76 patients.Univariate analysis showed that the diameter of the main pancreatic duct and the texture of the pancreas were the related factors affecting the occurrence of pancreatic fistula after PD (P<0.05), and the soft pancreas was the independent risk factor for the occurrence of pancreatic fistula after PD (OR=3.886, P=0.011). There was no significant difference in the incidence of postoperative pancreatic fistula between the internal drainage group and the external drainage group (P>0.05). There was no pancreatic fistula occurred in the patients with negligible risk. The incidence of postoperative pancreatic fistula in patients with high risk of external drainage group was only 12.5%, comparing with patients in internal drainage group (63.6%), the difference was statistically significant (P=0.026). There was no significant difference in the incidence of postoperative pancreatic fistula between patients in the external drainage group with moderate risk and low risk compared with the corresponding patients in the internal drainage group (P>0.05). Conclusions Pancreatic texture was an independent risk factor for pancreatic fistula after PD. External drainage maybe more effective than internal drainage in preventing pancreatic fistula after PD in patients with high risk of FRS.