The relationship between telomere length and stroke was inconsistent mostly due to different pathogenesis of subtypes, environment and genetics. We aimed to assess whether leukocyte telomere contributes to stroke in Southern Chinese by investigating a case-control study comprising 543 cases (224 atherothrombotic stroke, 94 hemorrhagic stroke and 225 lacunar infraction) and 616 controls and replicated the investigation in an independent study comprising 773 cases and 875 controls with the same diagnostic criteria. Telomere was inversely correlated with increasing age in controls (correlation coefficient γ = -0.28, P < 0.001) and in cases with atherothrombotic stroke (γ = -0.17, P = 0.012). Individuals within the lowest tertile of telomere showed a higher risk for atherothrombotic stroke [odds ratio 2.33, 95% confidence (CI) 1.42-3.83; P = 0.003], whereas had a lower presence of lacunar infarction (OR 0.49, 95% CI 0.30-0.81; P = 0.007). Similar results were obtained in the second replication study. A further meta-analysis showed a 12% increased pooled risk of ischemic stroke (95% CI 1.04-1.18) in relation to shorter telomere, but this association was stronger in the retrospective studies and in Asians when stratified by study design and ethnicity. Our data provided the first evidence that in Southern Chinese stroke population, leukocyte telomere is independently associated with atherothrombotic stroke and lacunar infarction.