Peripheral arterial disease (PAD) causes insufficient blood flow to the legs, which results in debilitating, activity-induced, ischemic pain (claudication). Claudication affects over 4 million individuals in the USA and limits the typical patient to walking = to 2 blocks before pain begins, with an associated functional capacity similar to that of patients with severe heart failure. Treadmill exercise training has been shown to be very effective at improving walking distance and functional status, with the prevailing theory that the training response is a result of adaptation in the lower extremity skeletal muscles. Although walking exercise may stimulate local skeletal muscle changes, ischemic pain (claudication) reduces the duration and intensity of exercise training tolerated, thus limiting conditioning of the cardiovascular system. Walking exercise also may result in ischemia-induced, short-term inflammatory responses. Aerobic arm ergometry, does not cause lower limb ischemia and associated pain, and thus may enable patients to achieve a greater amount of exercise training, resulting in a greater potential for cardiovascular conditioning. There is a clear need to determine the optimal training regimen for improving walking distance in men and women with claudication and to determine the effects of different exercise modalities on selected factors that influence improvement. Since women with claudication have historically been underrepresented in exercise training studies; it is not known whether the response to exercise training differs between men and women. The purpose of this study is to 1) Determine the relative efficacy of 12 weeks of aerobic arm versus treadmill exercise training, as compared to usual care (controls), on pain free walking distance (PFWD) and maximal walking distance (MWD), in 150 men and women with claudication, at immediate (12 weeks) and short-term follow-up (24 weeks), adjusting for unsupervised exercise, smoking, and diabetes status; 2) Determine the relative effectiveness of arm ergometry versus treadmill exercise training on cardiorespiratory and vascular factors that contribute to improvement in walking distance; 3) Determine the relative efficacy of arm ergometry or treadmill training versus usual care on health and functional outcomes; 4) Evaluate the response to exercise training independently for men and women. Assessments of walking distance, cardiovascular function, limb blood flow, and health and functional status will occur at baseline, after 6 and 12 weeks of training, and after 12 weeks of follow-up (24 weeks). It is hypothesized that 1) participants undergoing upper or lower extremity aerobic training will show similar superior improvement in walking distances and health and functional outcomes in comparison to control participants in walking distances as well as health and functional outcomes; and that 2) improvements in physiologic measures will be associated with improvements in walking distance. This will provide evidence to link the clinical outcomes seen with exercise training to specific physiologic factors, providing direction for future studies to determine the optimal exercise intervention in this population. PUBLIC RELEVANCE: Peripheral arterial disease affects more than 8 million Americans and is associated with significant morbidity, mortality, and debilitation, including activity-induced leg pain (claudication). Supervised exercise training using treadmill walking, although painful, is effective at reducing claudication, allowing persons with claudication to complete daily activities, including walking, with less pain. This study will determine the efficacy of aerobic arm exercise to reduce symptoms of claudication and improve walking ability. If effective, this type of exercise would offer a pain free therapeutic exercise alternative for individuals with claudication.