We sought to determine outcomes in patients with and without symptomatic cerebrovascular disease (sCVD) undergoing heart transplantation. Second, we sought to determine factors associated with stroke in the perioperative period after heart transplantation. sCVD is considered a relative contraindication to heart transplantation. Despite this concern, outcomes in patients with sCVD undergoing heart transplantation have not been well defined. Data on all single-organ heart transplants performed in the United States between April 1994 and December 2006 in patients age 40 years or older were analyzed. Survival analysis was performed to examine the effect of sCVD on the combined outcome of stroke or death, stroke, death, and functional decline, adjusting for potential confounding variables over long-term follow-up. In a separate analysis, predictors of perioperative stroke during the transplant-related hospitalization were examined using multiple logistic regression. There were 1,078 patients with and 16,765 patients without sCVD. The annualized rates of stroke or death (11.5% vs. 7.8%; p < 0.001), stroke (4% vs. 1.4%; p < 0.001), death (8.9% vs. 7.4%; p < 0.001), and functional decline (3.7% vs. 3.0%; p = 0.002) were higher in patients with sCVD than in patients without sCVD. In multivariable analysis, patients with sCVD were at increased risk of stroke or death (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.17 to 1.42), stroke (HR: 2.24; 95% CI: 2.02 to 2.87), and functional decline (HR: 1.21; 95% CI: 1.03 to 1.42) compared with those without sCVD. We did not identify a higher risk of death in patients with sCVD (HR: 1.08; 95% CI: 0.98 to 1.20), compared with those without sCVD. sCVD, ventilator use, and ventricular assist device use were the most important predictors of perioperative stroke. Patients with sCVD are at an increased risk of stroke and functional decline after transplantation independent of other variables, but not death, during long-term follow-up. These results should assist programs in making informed decisions in patients with sCVD who are undergoing evaluation for heart transplantation.