Selected near-infrared spectroscopy (NIRS) parameters were assessed in healthy untrained participants and in peripheral arterial disease (PAD) trained patients to evaluate their usefulness in rehabilitative outcome. Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks. Healthy participants performed their usual activities. Patients with PAD performed 2 home-based programs: structured at prescribed pace (S-pre, n = 31) and unstructured at free pace (U-free, n = 14). We measured ankle-brachial index (ABI), NIRS calf oxygen consumption at rest, NIRS dynamic muscle perfusion during an incremental test, and walking capacity. In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants. Among PAD, only S-pre group showed significant improvements in hemodynamic, functional, and NIRS parameters with selective adaptations in the worse legs. The assessment of NIRS parameters, that were found stable without training in healthy and modified in PAD only following structured training, might outline the local exercise-induced adaptations.