Acute pro-myelocytic leukemia (APML) is associated with an elevated risk of bleeding and thrombosis due to disseminated intravascular coagulation that is frequently present prior to initiation of therapy. We report the case of a 13 year-old male with Trisomy 21 diagnosed with APML found to have an asymptomatic aortic valve thrombus who developed a thromboembolic arterial ischemic stroke. Endovascular thrombectomy (EVT) restored cerebral circulation and a fibrin thrombus containing APML cells was retrieved. The patient made a neurologic recovery, nearing his baseline within one week post-EVT. We highlight that thromboembolic stroke can be a rare complication in APML and present unique management challenges.