The relationship between ankle-brachial index (ABI) remains uncertain relative to clinical and angiographic features of critical limb ischemia (CLI). From July 2011 to February 2013, 89 consecutive patients with CLI had non-invasive testing for indications of rest pain (n=23, 26%), as well as minor (n=29, 33%) and major (n=37, 42%) ischemic tissue loss. All patients subsequently underwent ABI testing and lower extremity angiography with visualization of the infragenicular arteries. Toe-brachial index (TBI) testing was available among 31 of these patients. Among patients with any ischemic tissue loss, 29% had an ABI between 0.7 and 1.4. Patients with rest pain alone had reduced odds of abnormal arterial runoff in univariate (OR 0.75, 95% CI 0.63-0.90; p=0.002) but not multivariate (p=0.50) analysis. Advanced age, increased ABI, reduced creatinine clearance, hyperlipidemia, and prior coronary artery disease were predictive of abnormal infragenicular runoff. Despite limitations in statistical power, median TBI, compared to ABI, tended to increase when infragenicular arterial runoff was preserved. Overall, the association of TBI with abnormal runoff was not significant (p=0.38). In conclusion, in the evaluation of CLI, nearly one-third of patients with any ischemic tissue loss had a normal or mildly reduced ABI. Assessment of TBI may augment the diagnostic accuracy of ABI in the evaluation of CLI.