© 2017 American College of Cardiology Foundation Objectives This study sought to evaluate predictors of stroke during left ventricular assist device (LVAD) support from data available prior to implantation, and quantify stroke-related morbidity and mortality. Background Stroke is a major complication after LVAD. Pre-implant factors that influence stroke are not well understood. Methods We evaluated all patients in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were implanted with continuous flow LVADs from May 1, 2012, to March 31, 2015. Pre-operative risk factors for stroke and stroke incidence, morbidity, and mortality were analyzed. Results During the study period, 7,112 patients underwent continuous flow LVAD placement. Median follow-up was 9.79 months (range 0.02 to 34.96 months). Of all patients, 752 (10.57%) had at least 1 stroke, with an incidence rate of 0.123 strokes per patient-year. A total of 447 (51.38%) strokes were ischemic and 423 (48.62%) were hemorrhagic. Patients with hemorrhagic stroke had worse survival than those with ischemic strokes (30-day survival: 45.3% vs. 80.7%; p < 0.001). Of patients with a first stroke, 13% had a second stroke. Pre-implant predictors of stroke were female sex (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.25 to 1.82; p < 0.001), pre-implant systolic blood pressure (HR: 1.01; 95% CI: 1.00 to 1.01; p = 0.002), heparin-induced thrombocytopenia (HR: 3.68; 95% CI: 1.60 to 8.47; p = 0.002), intra-aortic balloon pump (HR: 1.21; 95% CI: 1.01 to 1.46; p = 0.043), and primary cardiac diagnosis (ischemic/other/unknown) (p = 0.040). Conclusions Despite improvements in LVAD technology, stroke-related morbidity and mortality is substantial. Further investigation is necessary to decrease the risk of this devastating complication.