We investigated the burden of frailty across the spectrum of ankle-brachial index (ABI < 0.9, 0.9 ≤ ABI < 1.1, 1.1 ≤ ABI < 1.4 and ≥1.4) using data from the National Health and Nutritional Examination Survey (NHANES) in respondents aged >50 years. Criteria used to identify frailty status included weight loss, slow walking speed, weakness, exhaustion, and low physical activity. Participants meeting 1 to 2 criteria were classified as prefrail, and those meeting ≥3 criteria were classified as frail. Prevalence of frailty in respondents with ABI < 0.9 (17.5%) and 0.9 ≤ ABI < 1.1 (6.7%) was higher than in participants with normal ABI-1.1 ≤ ABI < 1.4 (4.7%). In multivariable multinomial logistic regression models, ABI < 0.9 predicted frailty (odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.08-4.94) and prefrailty (OR = 1.36, 95% CI = 0.90-2.07). Higher prevalence of frailty was seen in participants with ABI ≥ 1.4 (7.3%), P = .39. Frailty predicted general and cardiovascular mortality in participants with ABI < 0.9. Frailty mediates increased morbidity and mortality seen in peripheral arterial disease (PAD).