Large vessel peripheral arterial disease (LV-PAD) is a common condition that causes significant morbidity and disability. The authors evaluated the individual components of a comprehensive noninvasive vascular examination to identify the most sensitive and specific measurements for diagnosing LV-PAD. This cohort, initially screened between 1979 and 1981 in Rancho Bernardo, California, included 421 normal subjects and 63 subjects with LV-PAD. Segmental blood pressure ratios and flow velocities by Doppler ultrasound were used to define cases of LV-PAD. The sensitivity, specificity, positive predictive value, and negative predictive value of each individual component of the diagnostic algorithm were determined. Overall, measurements of posterior tibial flow showed the highest sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. In addition, an absent or non-recordable posterior tibial peak forward flow, occurring in 96% of all limbs with isolated posterior tibial disease, or an ankle ratio < or = 0.8 considered in parallel yielded a test with sensitivity of 89%, specificity of 99%, positive predictive value of 90%, negative predictive value of 99%, and overall accuracy of 98%. These results indicate that the vast majority of LV-PAD cases can be detected with a single measurement using a handheld Doppler flowmeter employed at the ankle.