Purpose Claudication is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). Differential diagnosis of PAD and LSS is often difficult due to the subjective natures of symptoms and atypical signs. The authors aimed to determine the usefulness of ankle-brachial index (ABI) measurement for the differential diagnosis of PAD and LSS when the etiology of claudication is uncertain. Methods Forty-two consecutive patients who had been referred by spine surgeons to a lower extremity vascular surgeon for atypical claudication were retrospectively analyzed. Atypical claudication was defined as claudication not caused by PAD, as determined by clinical manifestations, or by LSS, as determined by MR imaging. A final diagnosis of PAD was established by CT angiography (CTA) and of LSS by excluding PAD. Diagnostic validity of ABI for PAD in atypical presentation was assessed. Results Sixty-two legs of 42 atypical claudication patients were analyzed. Mean patient age was 65.8 ± 8.2 years (38-85) and 29 (69.0%) had diabetes mellitus. Mean ABI was 0.73 ± 0.14 (0.53-0.94) in the PAD group and 0.92 ± 0.18 (0.52-1.10) in the LSS group (P \ 0.001). Of the 33 legs with a low ABI (ABI \ 0.9), 29 legs were diagnosed as true positives for PAD by CTA and 4 were false positives, and of the 29 legs with a high ABI, 5 were false negatives and 24 were true negatives. The sensitivity and specificity of ABI for the diagnosis of PAD in patients with atypical claudication were 85.3 and 85.7%, respectively, and its positive and negative predictive values were 87.9 and 82.8%. Conclusions ABI is a recommended screening test for the differential diagnosis of lower leg claudication when clinical symptoms are atypical.