Simple SummaryOutcomes for patients with acute promyelocytic leukemia (APL) have improved over the past 40 years due to the development of targeted treatment regimens and an expanded understanding of the unique complications arising from both the disease and its treatments. Despite these advances, clinically significant bleeding and/or thrombosis in the first 30 days of treatment remain the most common causes of morbidity and mortality. Moreover, there is a lack of large clinical trials investigating approaches for the prevention and treatment of these complications. This review aims to provide a comprehensive overview and update on the coagulopathy associated with APL, compile current best practices for optimal management, and establish areas of potential future investigation to further improve outcomes for patients with APL.AbstractAcute promyelocytic leukemia (APL) has a well-established mechanism and a long-term prognosis that exceeds that of any other acute leukemia. These improving outcomes are due, in part, to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two targeted and highly active agents in this disease. However, there remains a considerable morbidity and mortality risk in APL secondary to clinically significant hemorrhagic and/or thrombotic events. Prevention and treatment of these coagulopathic complications remain significant impediments to further progress in optimizing outcomes for patients with APL. Moreover, the relative rarity of APL hinders adequately powered randomized controlled trials for evaluating APL coagulopathy management strategies. This review draws from peer-reviewed works falling between initial descriptions of APL in 1957 and work published prior to January 2023 and provides an updated overview of the pathophysiology of hemorrhagic and thrombotic complications in APL, outlines risk stratification parameters, and compiles current clinical best practices. An improved understanding of the pathophysiologic mechanisms driving hemorrhage and thrombosis along with the completion of well-designed trials of management strategies will assist clinicians in developing interventions that mitigate these devastating complications in an otherwise largely curable disease.