OBJECTIVE To determine the effect of metabolic syndrome components on intermittent claudication, physical function, health-related quality of life, and peripheral circulation in patients with peripheral arterial disease (PAD), and to identify the metabolic syndrome components most predictive of each outcome measure. METHODS Patients limited by intermittent claudication with three (n = 48), four (n = 45), or five (n = 40) components of metabolic syndrome were studied. Patients were assessed on PAD-specific measures consisting of ankle-brachial index (ABI), initial claudication distance, absolute claudication distance, physical function measures, health-related quality of life, and calf blood flow and transcutaneous oxygen tension responses after 3 minutes of vascular occlusion. RESULTS Initial claudication distance (mean +/- SD) progressively declined (P = .019) in those with three (203 +/- 167 m), four (124 +/- 77 m), and five (78 +/- 57 m) metabolic syndrome components, and absolute claudication distance progressively declined (P = .036) in these groups as well (414 +/- 224 m vs 323 +/- 153 m vs 249 +/- 152 m, respectively). Furthermore, compared with patients with only three components of metabolic syndrome, those with all five components had impaired values (P < .05) for peak oxygen uptake, ischemic window, 6-minute walk distance, self-perceived walking ability and health, daily physical activity, health-related quality of life on six of eight domains, calf hyperemia, and calf ischemia after vascular occlusion. Abdominal obesity was the predictor (P < .05) of exercise performance during the treadmill and 6-minute walk tests, as well as physical activity. Elevated fasting glucose was the predictor (P < .05) of peripheral vascular measures, self-perceived walking ability and health, and health-related quality of life. CONCLUSIONS PAD patients with more metabolic syndrome components have worsened intermittent claudication, physical function, health-related quality of life, and peripheral circulation. Abdominal obesity and elevated fasting glucose are the metabolic syndrome components that are most predictive of these outcome measures. Aggressively treating these metabolic syndrome components may be particularly important in managing symptoms and long-term prognosis of PAD patients.