BACKGROUND: Few medical therapies improve lower extremity functioning in people with lower extremity peripheral artery disease (PAD). Among people with PAD, we studied whether a group-mediated cognitive behavioral intervention promoting home-based unsupervised exercise prevented mobility loss and improved functional performance compared to control. METHODS AND RESULTS: One hundred ninety-four PAD participants were randomized. During months 1 to 6, the intervention group met weekly with other PAD participants and a facilitator. Group support and self-regulatory skills were used to help participants adhere to walking exercise. Ninety-percent of exercise was conducted at or near home. The control group attended weekly lectures. During months 6 to 12, each group received telephone contact only. Primary outcomes have been reported. Here we compare changes in exploratory outcomes of mobility loss (the inability to climb a flight of stairs or walk one-quarter mile without assistance), walking velocity, and the Short Physical Performance Battery. Compared to controls, fewer participants randomized to the intervention experienced mobility loss at 6-month follow-up: 6.3% versus 26.5%, P=0.002, odds ratio=0.19 (95% CI=0.06 to 0.58) and at 12-month follow-up: 5.2% versus 18.5%, P=0.029, odds ratio=0.24 (95% CI=0.06 to 0.97). The intervention improved fast-paced 4-m walking velocity at 6-month follow-up (P=0.005) and the Short Physical Performance Battery at 12-month follow-up (P=0.027), compared to controls. CONCLUSIONS: In exploratory analyses, a group-mediated cognitive behavioral intervention promoting unsupervised walking exercise prevented mobility loss and improved functioning at 6- and 12-month follow-up in PAD patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00693940.