Our previous study showed that the patients with more metabolic risk factors had higher risk of high ankle-brachial index (ABI), but the relationship between high ABI and the risk of severe cardiovascular and cerebrovascular diseases is still under debate. This study aims to evaluate this association in the general population. 1486 subjects of South China were recruited in the study. 61 subjects were defined as high ABI group (ABI≥1.3) and 65 subjects were randomly selected as normal ABI group (0.9<ABI<1.3). Biochemical parameters, clinical characteristics and 10-year hard coronary heart disease (HCHD) Framingham Risk Score (FRS) were compared between two groups. The results showed that the 10-year HCHD FRS of high ABI group was significantly higher than normal ABI group (7.87 ± 6.11 vs. 3.98 ± 2.90%, P<0.001). There was a positive correlation between ABI value and HCHD FRS in overweight participants (R = 0.576, P<0.01). The prevalence of ischemic stroke was higher in high ABI group than normal ABI group (21.3% vs. 6.2%, P<0.05), and it was higher in participants with HCHD FRS ≥ 6% than those with HCHD FRS<6% (19.1% vs. 6.9%, P<0.05). Moreover, the prevalence of ischemic stroke was higher in participants with high ABI and HCHD FRS ≥ 6% than those with normal ABI and HCHD FRS<6% (26.7% vs. 4.1%, P<0.05). BMI, hypertension, hsCRP and smoking were proved to be the independent factors and effective predictors for high ABI (P<0.05). In conclusion, high ABI combined with high HCHD FRS should be a potential predictor of ischemic stroke in the general population of South China.