Development of stroke while on left ventricular assist device (LVAD) support can be a source of significant morbidity and mortality. From March 2006 through November 2011, one hundred patients with chronic heart failure underwent implantation of a HeartMate II (HM II) LVAD (Thoratec Corp.) as a bridge to transplant (BTT; n = 65) or destination therapy (DT; n = 35). Records were reviewed to determine the prevalence and type of postimplant stroke, anatomic cerebral location of strokes, and associated morbidity and mortality. Cox multivariate logistic regression analysis was conducted to identify independent predictors of postoperative stroke. Strokes occurred in 12 patients (12.0%): four embolic and eight hemorrhagic. Median duration of support at the time of stroke was 281.0 days for embolic strokes and 380.5 days for hemorrhagic strokes (p = 0.028). Stroke patients had a significantly higher incidence of diabetes (66.7% vs. 40.9%; p = 0.024), history of preimplant stroke (16.7% vs. 4.5%; p = 0.046), and aortic cross-clamping with cardioplegic arrest during their LVAD implant (50.0% vs. 20.2%; p = 0.034) compared with patients without postoperative strokes. Mean international normalized ratio (INR) at the time of stroke was subtherapeutic in all four patients with embolic strokes (mean: 1.5 ± 0.1 IU; range 1.3–1.6 IU) and supratherapeutic in four of eight patients with hemorrhagic strokes (mean: 3.2 ± 2.2 IU, range: 1.4–7.0 IU; p = 0.024). There was a 25.0% 30 day mortality after stroke. Diabetes (odds ratio [OR] 6.36; p = 0.029), aortic cross-clamping with cardioplegic arrest (OR 4.75; p = 0.025), duration of LVAD support (OR 1.00; p = 0.008), and INR (OR 4.42; p = 0.020) were independent predictors of stroke in multivariate analysis with a trend toward significance for history of stroke (OR 6.25; p = 0.075). Stroke represented an important source of morbidity and mortality for patients on HM II LVAD support. As long-term device therapy continues to gain popularity for both BTT and DT, a better understanding of the predictors of stroke, more strict control of postoperative anticoagulation, and the establishment of a risk stratification model may aid in minimizing its occurrence.