Using data from the Multi-Ethnic Study of Atherosclerosis (United States, 2000-2015), 6,527 racially/ethnically diverse adults (mean age, 62 (standard deviation, 10) years) free of known cardiovascular (CVD) had ankle brachial index (ABI) assessment of their bilateral dorsalis pedis/posterior tibial arteries (4 vessels total) and were followed for total mortality and incident CVD events/mortality. Individuals were classified into categories of 0-, 1-, 2-, 3- or 4-vessel peripheral artery disease (PAD) (ABI of ≤0.9). There were 1,202 deaths (18%), 656 incident CVD events (10%), and 282 CVD deaths (4.3%). Of the 6,527 individuals, 5,711 (87.5%) had 0-, 460 (7.0%) had 1-, 218 (3.3%) had 2-, 69 (1.1%) had 3-, and 69 (1.1%) had 4-vessel PAD, respectively. In multivariable Cox models, higher number of vessels with PAD was associated with higher risk of mortality (P for trend <0.001), CVD events (P for trend = 0.002), and CVD mortality (P for trend = 0.001). Compared with individuals who had 0-vessel disease, hazard ratios for mortality were 1.29 (95% confidence interval (CI): 1.06, 1.59) for 1-, 1.45 (95% CI: 1.14, 1.86) for 2-, 1.58 (95% CI: 1.13, 2.21) for 3-, and 2.15 (95% CI: 1.58, 2.94) for 4-vessel disease. A similar pattern was seen for CVD events/mortality. These results suggest the importance of accounting for ABI values of all 4 leg arteries in clinical practice and research.