Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and is associated with increased cardiovascular morbidity and mortality. We describe the prevalence and risk factors of PAD in a multi-ethnic Asian population (Chinese, Malays and Indians) in Singapore. The Singapore Prospective Study Program recruited 4132 individuals between 2004 and 2006 in which the ankle-brachial index (ABI) was measured using the Smartdop™ 20EX bi-directional blood flow detector. PAD was defined as ≤ 0.9 and a high ABI > 1.4, with ABI 1.11-1.20 as reference. The mean age (SD) of individuals in the study was 49.9 (11.8) years, with 51.8% females. PAD was present in 4.3% of the population and a high ABI (> 1.4) was rare. Malays and Indians had a higher risk (especially in females). Compared to those with an ABI between 1.11 and 1.20, those with PAD were more likely to be of Malay and Indian ethnicity, female sex, with higher systolic blood pressure and pulse pressure, with increased prevalence of diabetes mellitus, hypertension, albuminuria and renal impairment, and with a past history of stroke. In conclusion, in this large multi-ethnic Asian population, we document the distribution and risk factor associations for PAD. PAD shows an ethnic distribution similar to that of coronary artery disease in Singapore, with differences in sex distribution. Apart from traditional vascular risk factors, pulse pressure, renal impairment and a past history of stroke are important determinants of PAD.