Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease. We examined 565 men and women (average age, 66 years) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques--measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound. We identified 67 subjects with the disease (11.9 percent), whom we followed prospectively for 10 years. Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compared with 31 of the 183 men (16.9 percent) and 26 of the 225 women (11.6 percent) without evidence of peripheral arterial disease. After multivariate adjustment for age, sex, and other risk factors for cardiovascular disease, the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 (95 percent confidence interval, 1.9 to 4.9) for deaths from all causes, 5.9 (95 percent confidence interval, 3.0 to 11.4) for all deaths from cardiovascular disease, and 6.6 (95 percent confidence interval, 2.9 to 14.9) for deaths from coronary heart disease. The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease. After the exclusion of subjects who had a history of cardiovascular disease at base line, the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated. Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic. Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes.