Background: Peripheral arterial disease (PAD) in the presence of a normal ankle-brachial index (ABI) can be diagnosed noninvasively by measuring a postexercise ABI or by measuring the toe-brachial index (TBI). Methods: This was a prospective comparative study. Over a period of 30 months, a total of 415 patients who were referred with the suspicion of vascular claudication and resting values of 0.91 ≤ ABI1.10 (P ≤ 0.022 for both), but there were no statistically significant differences found in other ABI intervals (P > 0.200 for all). Conclusions: The magnitude of the TBI reduction correlates with an increased probability of an abnormal postexercise ABI. However, this is due in part to limbs with a low TBI having a lower resting ABI on average than limbs with a normal TBI, which also correlates with the probability of an abnormal exercise test result. This study shows that the TBI and the postexercise ABI are not interchangeable for establishing a PAD diagnosis.