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Objective: To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score., Background: POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance., Methods: Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed., Results: A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created., Conclusions: The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.