Predictors of future stroke events gain importance in vascular medicine. Herein, we investigated the value of the ankle-brachial index (ABI), a simple non-invasive marker of atherosclerosis, as stroke predictor in addition to established risk factors that are part of the Framingham risk score (FRS).4299 subjects from the population-based Heinz Nixdorf Recall study (45–75 years; 47.3% men) without previous stroke, coronary heart disease or myocardial infarcts were followed up for ischemic and hemorrhagic stroke events over 109.0 ± 23.3 months. Cox proportional hazard regressions were used to evaluate ABI as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, LDL, HDL, diabetes, smoking).104 incident strokes (93 ischemic) occurred (incidence rate: 2.69/1000 person-years). Subjects suffering stroke had significantly lower ABI values at baseline than the remaining subjects (1.03 ± 0.22 vs. 1.13 ± 0.14, p < 0.001). In a multivariable Cox regression, ABI predicted stroke in addition to classical risk factors (hazard ratio = 0.77 per 0.1, 95% confidence interval = 0.69–0.86). ABI predicted stroke events in subjects above and below 65 years, both in men and women. ABI specifically influenced stroke risk in subjects belonging to the highest (>13%) and intermediate (8–13%) FRS tercile. In these subjects, stroke incidence was 28.13 and 8.13/1000 person-years, respectively, for ABI < 0.9, compared with 3.97 and 2.07/1000 person-years for 0.9 ≤ ABI ≤ 1.3.ABI predicts stroke in the general population, specifically in subjects with classical risk factors, where ABI identifies subjects at particularly high stroke risk.