Objective: To investigate the influential factors and prediction for early postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), so as to guide the earlier removal of abdominal drainage tube to accelerate postoperative recovery of the patients. Methods: The clinical data of 430 patients undergoing PD in Southwest Hospital from January 2013 to October 2015 were reviewed. The risk factors and their predictive values for early POPF were analyzed by univariate and multivariate statistical analysis, and receiver operating characteristic (ROC) curve, respectively. Results: Early POPF occurred in 116 patients (26.9%) of the total 430 patients. In addition, among the patients without early POPF, the incidences of POPF, intra-abdominal infections and overall complications were all significantly reduced in those with abdominal drainage tube removed within postoperative day (POD) 5 compared with others with abdominal drainage tube retained more than POD 5 (3.1% vs. 12.1%; 9.2% vs. 20.3%; 24.5% vs. 42.0%, all P<0.05). The results of univariate and multivariate Logistic regression analysis showed that drain fluid amylase on POD 1 (DFA1) and serum amylase on POD 1(SA1) were independent risk factors for early POPF following PD (OR=1.000 and 1.004, 95% CI=1.000–1.001 and 1.001–1.006, both P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of DFA1 for predicting early POPF was 0.916 which was obviously larger than that of SA1 (0.745), and the sensitivity, specificity, and the positive and negative predictive value were 91.7%, 80.8%, 62.7%, and 96.5% for DFA1≥494.75 IU/L, respectively. Conclusion: DFA1 is an important risk and predictive factor for early POPF after PD. In patients with DFA1<494.75 IU/L, the abdominal drainage tube can be safely removed and then fast track recovery protocol can be adapted on POD 3.