Objective: To investigate the risk factors of pancreatic fistula after resection of pancreatic body and tail duct adenocarcinoma. Methods: all cases of pancreatic body and tail resection for pancreatic body and tail duct adenocarcinoma in Union Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from January 2016 to December 2018 were analyzed retrospectively in a single center. The preoperative, intraoperative and postoperative data were collected and analyzed by spssv22.0. The definition and grouping of pancreatic fistula were implemented according to the standards formulated by the international pancreatic fistula research group in 2016. All cases were followed up for at least 3 months. Results: A total of 91 cases were included in the study. The overall pancreatic fistula rate was 25.27% (23/91). No death occurred within 90 days after operation. Three risk factors for pancreatic fistula were identified: Pancreatic texture (soft) [odds ratio = 8.965,95% confidence interval (2.400,33.490), p = 0.001], combined with cardiovascular disease [odds ratio = 9.148,95% confidence interval (1.936,43.225), p = 0.05], albumin <26.50g/l[odds ratio =6.100,95% confidence interval (1.846,20.157), p = 0.003]. Conclusion soft pancreas, complicated with cardiovascular disease and low albumin level on the first day after operation are independent risk factors for pancreatic fistula after operation of pancreatic duct adenocarcinoma. Due to the limitations of the study, the results need to be further verified.