ABSTRACT: Background Ankle-brachial indexes (ABI) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assigned a normal ABI when the result would be abnormal if calculated using one of the other blood pressure readings. Cardiovascular outcomes for patients with discordant ABIs are undescribed. Methods and Results We performed a retrospective study of patients who underwent ABI measurement for any indication between January 1996 and June 2018. Those with normal ABIs (1.00-1.39) were included. We compared patients with all 4 normal ABIs (calculated using all 4 ankle arteries; n=15 577, median age 64.0 years, 54.4% men) to those with discordant ABIs (at least 1 abnormal ABI ?0.99; n=2095, median age 66.0 years, 47.8% men). The outcomes assessed were ischemic stroke, myocardial infarction, and all-cause mortality. Compared with patients with concordant normal ABIs, patients with discordant ABIs were older; women; smoked; and had chronic kidney disease, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, hypertension, or prior stroke. Patients with discordant ABIs had a greater risk of myocardial infarction (hazard ratio [HR], 1.31; 95% CI, 1.10-1.56), ischemic stroke (HR, 1.53; 95% CI, 1.37-1.72), and all-cause mortality (HR, 1.27; 95% CI, 1.16-1.39), including after adjustment for baseline comorbidities. Conclusions Discordant ABI results were associated with an increased risk of myocardial infarction, stroke, and all-cause mortality in the studied population. Clinicians should examine ABI calculations using all 4 ankle arteries to better characterize a patient's cardiovascular risk.