Background The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown. Methods Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high ABI groups (ABI > 1.3, >1.4, and >1.5) and compared the risk factor profile and CVD event rates of the normal ABI group to each high ABI group. Results The prevalence of high ABI was 5.5% for ABI > 1.3, 1.2% for ABI > 1.4, and 0.37% for ABI > 1.5. Compared with participants with a normal ABI, those with ABI > 1.3 had a lower prevalence of hypertension and current smoking. The ABI > 1.3 group had a greater mean body mass index, but was characterized by fewer pack years of smoking and lower systolic and diastolic blood pressures than the normal ABI group. The prevalence of diabetes, left ventricular hypertrophy, claudication, and coronary heart disease and mean values of fibrinogen, factor VIII activity, von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial thickness were similar between the two ABI groups. The risk factor profiles of the ABI > 1.4 and >1.5 groups were also not statistically significantly different from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the normal ABI group, 7.6 in the ABI > 1.3 group, 7.6 in the ABI > 1.4 group, and 7.4 in the ABI > 1.5 group. The CVD event rates of the high ABI groups were similar to that of the normal ABI group. Conclusion Individuals with a high ABI are not characterized by a more adverse atherosclerosis risk factor profile and do not suffer greater CVD event rates than those with a normal ABI.