Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Endothelium-dependent vasoreactivity, which is advocated as a measure of vascular health, is impaired in persons with cardiac risk factors and coronary artery disease. Few studies have examined the degree of endothelial dysfunction in patients with PAD. Using high-resolution external vascular ultrasound, we measured brachial artery diameter and flow at rest, and in response to reactive hyperemia (flow-mediated dilation) in 50 older patients (age 69 +/- 1 year) with PAD (ankle-to-brachial artery index of 0.67 +/- 0.03), and 50 age-matched non-PAD patients. Coronary artery disease was more prevalent in PAD than in non-PAD patients (40% vs 4%, p <0.001). Systolic blood pressure (153 +/- 4 vs 141 +/- 3 mm Hg, p <0.01), fasting glucose (129 +/- 6 vs 109 +/- 5 mg/dl, p <0.001), and pack-years smoked (54 +/- 7 vs 25 +/- 3, p <0.01) were higher in the PAD than in non-PAD patients. There were no differences in baseline brachial artery diameter, blood velocity, or flow between the 2 groups. However, the 1-minute postocclusion percent change in diameter (6.5 +/- 0.7% vs 9.8 +/- 0.7%, p <0.001) and the change in diameter (0.22 +/- 0.02 vs 0.33 +/- 0.02 mm, p <0.001) were lower in PAD than in non-PAD patients, suggesting impaired endothelium-dependent dilation. The postocclusion hyperemic velocity and blood flow were also lower in PAD than in non-PAD patients. In multiple regression analyses the low-density lipoprotein-to-high-density lipoprotein cholesterol ratio, elevated fasting glucose, and high systolic blood pressure were independent predictors of percent change in brachial artery diameter (r2 = 0.37, p <0.001). Thus, older patients with PAD had impaired endothelial dependent vasodilation compared with controls that was associated with the presence of cardiac risk factors. The effect of cardiac risk factor intervention on endothelial function in patients with PAD remains to be determined.