Background: Among coronary disease patients, concomitant peripheral arterial disease is a potent risk factor for future cardiac events and mortality. We sought to determine clinical and biochemical markers that might better elucidate the relationship between coronary and peripheral arterial disease. Methods: Two months after an index myocardial infarction, 1045 patients provided detailed medical histories and underwent blood testing for selected hemostatic, lipid, and inflammatory markers. Patients were then followed up prospectively for a mean of 26 months. Results: Compared with individuals without intermittent claudication (n = 966), those with claudication (n = 78) (information was unavailable for 1 individual) were significantly older and demonstrated an increased frequency of diabetes mellitus, tobacco use, prior cardiac and cerebrovascular events, and depressed left ventricular function. Individuals with claudication were less likely to receive β-blocker therapy after the index infarction. Individuals with claudication had evidence of enhanced procoagulant and proinflammatory states manifested by relative elevations in plasma fibrinogen, D-dimer, C-reactive protein, and serum amyloid A concentrations. During follow-up, the presence of claudication was associated with an independent 2-fold increase in the combined end point of death or nonfatal cardiac event (38.5% vs 17.8%, P = .001) and a 5-fold increase in cardiac mortality (19.2% vs 3.6%, P = .001). Patients with intermittent claudication who were not treated with β-blockers had a significant 3-fold mortality excess relative to those receiving β-blockers. Conclusions: Following myocardial infarction, the added presence of intermittent claudication is associated with heightened procoagulant and proinflammatory states and an underuse of β-blocker therapy and is a strong independent predictor of recurrent cardiovascular events.