Patients with peripheral arterial disease (PAD) who become symptomatic with claudication (approximately one-third of the population) have a marked impairment in exercise performance and overall functional capacity. Patients with claudication have a peak oxygen consumption measured during graded treadmill exercise testing that is 50% of that in age-matched normal subjects, and also report great difficulty in walking relatively short distances, even at a slow walking speed. The reduced walking capacity is associated with impairment in activities of daily living and quality of life. Thus, claudication is highly limiting to the physical functioning of daily activities. Improving mobility and improving the reduced quality of life are therefore major goals of treatment. Patients with PAD develop metabolic abnormalities in the skeletal muscles of the lower extremity. These abnormalities include impairment in ischemic muscle mitochondrial electron transport chain activity and accumulation of intermediates of oxidative metabolism (acylcarnitines). Patients with the greatest accumulation of muscle acylcarnitines have the most impaired exercise performance. Thus, claudication is not simply the result of reduced blood flow, and alterations in skeletal muscle metabolism are part of the pathophysiology of the disease. L-carnitine and propionyl-L-carnitine may improve the metabolism and exercise performance of ischemic muscles. L-carnitine in a dose of 2 grams twice daily improved treadmill performance, but propionyl-L-carnitine (an acyl form of carnitine) was more effective than L-carnitine in improving treadmill walking distance. In two multicenter trials of a total of 730 patients, initial and maximal treadmill walking distance improved more with propionyl-L-carnitine than placebo. The drug also improved quality of life and had minimal side effects as compared with placebo. Propionyl-L-carnitine has not been approved for use in the United States.