The authors studied associations between ankle-brachial index (ABI) and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis. Participants included 3,458 women (average age = 62.6 years) and 3,112 men (average age = 62.8 years) who were free of clinically evident cardiovascular disease. Measurements included ABI, carotid artery intima-media thickness, and coronary artery calcium assessed with computed tomography. Five ABI categories were defined: <0.90 (definite peripheral arterial disease (PAD)), 0.90-0.99 (borderline ABI), 1.00-1.09 (low-normal ABI), 1.10-1.29 (normal ABI), and > or =1.30 (high ABI). Compared with that in men with normal ABI, significantly higher internal carotid artery intima-media thickness was observed in men with definite PAD (1.58 vs. 1.09; p < 0.001), borderline ABI (1.33 vs. 1.09; p < 0.001), and low-normal ABI (1.18 vs. 1.09; p < 0.001) after adjustment for confounders. Fully adjusted odds ratios for a coronary artery calcium score greater than 20 decreased across progressively higher ABI categories in both women (2.85 (definite PAD), 1.27 (borderline ABI), 1.11 (low-normal ABI), 1.00 (normal ABI; referent), and 0.78 (high ABI); p for trend = 0.0002) and men (3.26 (definite PAD), 1.72 (borderline ABI), 1.14 (low-normal ABI), 1.00 (normal ABI; referent), and 1.43 (high ABI); p for trend = 0.0002). These findings indicate excess coronary and carotid atherosclerosis at ABI values below 1.10 (men) and 1.00 (women) and may imply increased risk of cardiovascular events in persons with borderline and low-normal ABI.