Atherosclerosis is a generalized disease with considerable overlap of its coronary, carotid, and peripheral manifestations. As an indicator of multifocal atherosclerosis, peripheral arterial disease (PAD) is emerging as an important aid in risk stratification of patients with coronary artery (CAD) or cerebrovascular disease (CVD). Therefore, the aim of the study was to assess the prevalence of PAD in high risk subjects and its ability to identify coronary or cerebrovascular patients. A total of 952 (63.3% male; age 63.7 +/-10.7 years) patients at high cardiovascular risk (>or=2 risk factors), or with evidence of CAD or CVD were screened for PAD by means of ankle-brachial index (ABI) assessment; 226 patients were at high risk (>or=2 risk factors), 575 had CAD, and 151 had CVD. A total of 42% of patients with CAD and 36% of patients with CVD had PAD. In patients with CAD one half of cases of PAD were asymptomatic. Asymptomatic PAD (pathological ABI) was strongly associated with CAD and CVD, even after adjustment for age, gender, and other risk factors. No significant differences between CAD, PAD, and CVD patients were observed in terms of risk profiles. In conclusion, our findings confirm a high prevalence of both symptomatic and asymptomatic PAD in patients at high cardiovascular risk and its association with both CAD and CVD.