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Introduction: Patients with systemic cancer often develop acute ischemic stroke from unique mechanisms, including cancer-mediated hypercoagulability, and their risk of recurrence is high. Conversely, stroke mechanisms in patients with primary brain tumors are incompletely understood, and the risk of recurrent thromboembolism in these patients is uncertain.Methods: We performed a retrospective cohort study of adult patients treated for a primary brain tumor at Memorial Sloan Kettering Cancer Center who were diagnosed with MRI-confirmed acute ischemic stroke from 2005 to 2015. Study neurologists used all available electronic records to collect data on patients’ cancer history, stroke risk factors, treatments, and outcomes. Stroke mechanisms, including the TOAST stroke subtype classification, were adjudicated by consensus. The primary outcome was recurrent thromboembolism (arterial or venous) and the secondary outcome was recurrent ischemic stroke. Kaplan-Meier survival statistics were used to calculate cumulative outcome rates, and multivariate Cox proportional hazards analysis was used to evaluate the association between several prespecified potential risk factors and outcomes.Results: We identified 83 patients with primary brain tumors and acute ischemic stroke. Median age was 60 years (IQR 51-67) and 53% were women. Tumors were mostly gliomas (72%) and meningiomas (13%). Prior head and neck radiotherapy was common (71%). Most strokes were from unconventional mechanisms, particularly radiation vasculopathy (36%) and surgical manipulation (19%). Small- or large-vessel disease or cardioembolism caused 13% of strokes, while 28% were cryptogenic. Median survival from index stroke was 2.2 years. Cumulative rates of recurrent thromboembolism were 11% at 30 days, 17% at 180 days, and 27% at 360 days; while cumulative rates of recurrent stroke were 5% at 30 days, 8% at 180 days, and 13% at 360 days. We found no significant predictors of outcomes, although radiation vasculopathy was nonsignificantly associated with recurrent stroke (HR 2.4, 95% CI 0.7-7.8).Conclusions: Patients with primary brain tumors generally develop strokes from unique mechanisms and their risk of recurrence is high.