Simple SummaryThe treatment of periampullary tumors is becoming increasingly multimodal. Surgical interventions must be weighed against alternative therapeutic options, including ablative radiation and systemic chemotherapy. An operation should not jeopardize the receipt of adjuvant therapies. Therefore, a multiparametric risk assessment is crucial for patients who are potential surgical candidates. If pancreatoduodenectomy (PD) is feasible, a series of perioperative checkpoints are keys to a rapid recovery. The aim of our review is to itemize the pre-, intra-, and post-operative pathways of PD, with the intent of providing clinicians with an up-to-date perioperative roadmap.AbstractPancreaticoduodenectomy (PD) is a mainstay in the management of periampullary tumors. Treatment algorithms increasingly employ a multimodal strategy, which includes neoadjuvant and adjuvant therapies. However, the successful treatment of a patient is contingent on the execution of a complex operation, whereby minimizing postoperative complications and optimizing a fast and complete recovery are crucial to the overall success. In this setting, risk reduction and benchmarking the quality of care are essential frameworks through which modern perioperative PD care must be delivered. The postoperative course is primarily influenced by pancreatic fistulas, but other patient- and hospital-associated factors, such as frailty and the ability to rescue from complications, also affect the outcomes. A comprehensive understanding of the factors influencing surgical outcomes allows the clinician to risk stratify the patient, thereby facilitating a frank discussion of the morbidity and mortality of PD. Further, such an understanding allows the clinician to practice based on the most up-to-date evidence. This review intends to provide clinicians with a roadmap to the perioperative PD pathway. We review key considerations in the pre-, intra-, and post-operative periods.