Recent data have implicated telomere-length shortening as potential risk predictor for vascular diseases, including stroke. However, to date, prospective epidemiological data are scarce in relation to ischemic stroke risk. Using leukocyte DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we examined the relationship of leukocyte telomere repeat copy number to single gene copy number (TSR), using a quantitative polymerase chain reaction protocol, amongst 259 white males who subsequently developed an ischemic stroke and amongst an equal number of age- and smoking-matched white males who remained free of reported vascular disease during follow up (controls). The observed TSRs were inversely correlated with age in the controls (p < 0.0001). However, the observed TSRs were similar between cases and controls (p = 0.92). In a multivariable adjusted analysis, no evidence was found for an association of the TSRs with ischemic stroke risk (odds ratio [OR] = 1.100, 95% confidence interval [CI], 0.506-2.392, p = 0.811). The present investigation has shown no evidence for an association of relative leukocyte telomere length with risk of incident ischemic stroke. More importantly, our present findings require replication/confirmation in future large, prospective studies.