Resting muscle VO2 consumption (rmVO2) as measured by near-infrared spectroscopy (NIRS) has been poorly studied in peripheral arterial disease (PAD). We studied the feasibility of its assessment in a clinical setting, compared values from PAD and healthy participants, and identified factors affecting rmVO2 in PAD. A total of 119 PAD patients with claudication and 30 healthy participants were enrolled. Ankle brachial index (ABI), adipose tissue thickness, and rmVO2 in the gastrocnemius after venous (rmVO2ven) or arterial (rmVO 2art) occlusion were measured with NIRS. Compared to rmVO 2art, rmVO2ven determination was less painful (P =.001), with higher values (P <.0001). rmVO2ven of PAD patients was not significantly different from healthy participants and was inversely correlated with the corresponding ABI (P =.018). rmVO2ven from severely diseased legs was higher than values from borderline/moderately diseased legs (P =.003). The determination of rmVO2ven by NIRS is suitable for the clinical setting and allows noninvasive quantification of a compensatory peripheral adaptation in patients with PAD. © 2010 The Author(s).