To evaluate usefulness of ankle-brachial index (ABI) in the screening for asymptomatic cervico-cerebral atherosclerosis (CCA) against traditional vascular risk assessment.This study included a random population sample of 933 Caucasians without prior cardiovascular disease but with a moderate and high vascular risk (REGICOR score 5–9% and ≥10%). Presence and degree of CCA was evaluated by color-coded duplex and significant stenosis >50% (SCCA) confirmed by MRA.Prevalence of significant carotid and/or intracranial stenosis was 6% in the whole population, but increased up to 25% among those subjects with ABI ≤0.9 regardless of REGICOR score. Using REGICOR ≥10%, the likelihood ratio (LR) for the detection of SCCA was 1.8, while using ABI ≤0.90 the LR was 6.0. After multivariate regression analysis, low ABI was independently associated with SCCA whereas REGICOR score was not. Less than 40% of subjects with SCCA were taking antiplatelet drugs or statins at the moment of diagnosis.ABI emerged as a useful and simple tool in identifying asymptomatic SCCA in our population. This finding may be important for improving stroke primary prevention strategies.