The goal of this study is to investigate the relationship between peripheral arterial disease and mortality in a large patient population and assess the effects of other atherosclerotic diseases, diabetes and smoking on this relationship. All patients, 50 years or older and with no history of lower extremity surgery, evaluated for lower extremity arterial disease in a university hospital peripheral vascular laboratory over a 13-year period (1977-1989) were included in the study (n = 1930). Arterial disease was assessed by measurement of the resting ankle brachial index (ABI) in these patients. The ABI was calculated by dividing the systolic pressure in the tibial arteries by the pressure in the brachial artery. Analyses of the data by use of multivariate statistical techniques and by stratification of the patient population by co-morbid condition indicate that ABI is a robust and independent predictor of all-cause mortality in both men (relative risk (RR) = 1.6, 95% confidence interval (CI) 1.3, 2.0) and women (RR = 1.9, 95% CI 1.4, 2.4). The relative risks are essentially unchanged after exclusion of all patients with clinical history of cardiovascular disease or diabetes. Similarly, a low ABI is an important risk factor for mortality among patients with a history of stroke, angina or diabetes; men and women with a history of smoking and women who are non-smokers. Therefore, the measurement of ABI, a simple, objective, non-invasive technique which can be used in the physician's office, may be useful for early identification of patients at high risk for morbidity and mortality.