Objective: To study neurologic complications after heart transplant. Design: Retrospective cohort study. Setting: Cardiac transplant program at Mayo Clinic, Rochester, Minnesota. Patients: We retrospectively studied 313 patients who underwent heart transplant at Mayo Clinic Rochester from January 1, 1988, through October 31, 2006. Main Outcome Measures: Neurologic symptoms, neurologic complications, score on the Glasgow Outcome Scale, and mortality. Results: Causes of end-stage heart failure were idiopathic dilated myopathy (34%), ischemic heart failure (29%), congenital disorders (12%), amyloidosis (11%), and miscellaneous (15%). Perioperative neurologic complications occurred in 23% of patients and included delirium or encephalopathy (9%), cerebrovascular complications (5%), and diseases of the peripheral nerves and muscles (4%); however, only perioperative cerebrovascular complications were associated with 1-year mortality (hazard ratio, 4.17;95%confidence interval, 1.04-16.76;P=.04). Most of these cerebrovascular complications occurred after the second postoperative day and were related to mechanical support of the circulation. Over 18 years, the risk for neurologic complications was 81%: sleeping disorders, 32%; polyneuropathy, 26%; and cerebrovascular diseases, 14%. Cause of death was neurologic in 12 of 95 patients (13%), and the most common were cerebrovascular disease (n=6) and central nervous system infectious diseases (n=3). Adjusting for baseline predictors, central nervous system infection (hazard ratio, 4.29; 95% confidence interval, 1.69-10.91; P=.002), depression (hazard ratio, 1.81; 95% confidence interval, 1.06-3.09; P=.03), and seizures (hazard ratio, 3.44; 95% confidence interval, 1.33-8.85; P=.01) were predictive for mortality. Conclusions: Perioperative neurologic complications are frequent in heart transplant recipients, but most are transient and inconsequential. However, perioperative stroke is the most important neurologic complication affecting survival in the first year after heart transplant. Infectious diseases of the central nervous system are associated with fatal outcome.