Background and Objective: Postoperative pancreatic fistula (POPF) is associated with a mortality of up to 25% apart from significant morbid sequelae related to abdominal sepsis and post pancreatectomy hemorrhage. Numerous strategies to curtail the risk of POPF and associated morbidity have been largely unsuccessful. The pancreaticoenteric anastomosis post pancreaticoduodenectomy in a high-risk pancreas represents a significant surgical and clinical challenge. In this narrative review, we present the strategies for early identification and comprehensive management of the high-risk pancreas as per the available literature and present a stepwise algorithmic approach of different fistula mitigation strategies in patients undergoing pancreaticoduodenectomy.Methods: Medline, PubMed, Embase, Cochrane Library, and various center-specific guidelines were searched for the pancreas, pancreatic cancer, pancreatectomy, pancreatoduodenectomy, Whipple's operation, postoperative, complications, fistula, High-risk pancreas, risk assessment, different predictors, and scoring systems for the high-risk pancreas, current and emerging concepts in the development of POPF and mitigation strategies management and treatment in various combinations.