Introduction Compared to bleeding, major thromboses are a less commonly encountered problem in acute promyelocytic leukemia (APL), and our knowledge about the epidemiology of major thromboses in APL stems mainly from individual case reports. The purpose of this study was to provide a better understanding of the epidemiology of APL-related thrombosis as a first step towards developing preventive strategies. Materials and methods We report a rare case of catastrophic acute myocardial infarction in a patient with APL while she developed the all-trans retinoic acid (ATRA) syndrome. We describe the pathogenesis of APL-related thrombosis and review all previously reported cases of major thromboses in APL. Results We found 94 cases of major thromboses in patients with APL. Both genders were almost equally affected. More than 80% of events occurred before or during induction therapy with deep vein thrombosis/pulmonary embolism (DVT/PE), cardiac events, and cerebrovascular accidents (CVA) constituting more than 75% of all cases. Arterial events were slightly more common than venous events. Only 2 arterial events occurred after completion of induction therapy. Thrombosis was associated with life-threatening hemorrhage in about 15%, significant coagulative defects in about 50%, and ATRA syndrome in about 13% of cases. Cardiac thrombotic events, DVT/PE, and CVA were associated with ATRA syndrome in 24%, 4.5%, and 5% of cases, respectively (p = 0.09). None of the observed trends and associations reached statistical significance. Conclusions This review advances our understanding of the epidemiology of major thromboses in APL. With accumulation of more cases in the literature, some of our results may become statistically significant.