Leukocyte counts predict incident cardiovascular disease, but little data are available on the relationship of leukocyte count to outcome after ischemic stroke. We hypothesized that leukocyte count at the time of incident ischemic stroke is associated with prognosis. Patients with first ischemic stroke were prospectively followed for 5 years for the occurrence of recurrent stroke, myocardial infarction (MI), or death. Cox proportional hazard models were constructed to estimate hazard ratios and 95% confidence intervals (CIs) for the effect of leukocyte count on outcomes after adjusting for other risk factors. Ischemic stroke patients (n = 655) were evaluated (mean age, 69.7 +/- 12.7 years; 45% men; 51% Hispanic, 28% black, and 19% white). Seventy percent of samples were drawn within 24 hours of stroke. Mean leukocyte count was 9.1 +/- 4.7 x 10(9)/L. Leukocyte count was a significant independent predictor of the 30-day risk of recurrent stroke, MI, or death after adjusting for age, sex, race/ethnicity, other risk factors, and stroke severity (adjusted hazard ratio per unit increase in leukocyte count, 1.07; 95% CI, 1.00 to 1.13). Leukocyte count was also a significant independent predictor of outcome events over 5 years (adjusted hazard ratio per unit increase in leukocyte count, 1.04; 95% CI, 1.00 to 1.07). Our findings indicate that elevated leukocyte count at the time of ischemic stroke predicts future recurrent stroke, MI, or death. Acute infectious complications of stroke or underlying inflammation could account for this association.