The most common cause of peripheral arterial disease is the buildup of plaque on the inside of arteries. Plaque is made up of excess cholesterol, calcium, and other substances in your bloodstream that, over time, build up along the inner walls of the arteries, including the arteries that feed your legs. The plaque deposits decrease the space through which oxygen- and nutrient-rich blood can flow. Poor blood flow "starves" the muscles and other tissues in the lower body. See a picture of peripheral arterial disease of the legs.

This process of plaque buildup-called atherosclerosis or "hardening of the arteries"-usually happens throughout the body, including the leg arteries, coronary arteries, and carotid arteries.

Atherosclerosis gradually develops over a lifetime. High cholesterol, high blood pressure, and smoking contribute to atherosclerosis and peripheral arterial disease. For more information on risk factors, see the What Increases Your Risk section of this topic. See pictures of atherosclerosis and how high blood pressure damages arteries.

In very rare cases, peripheral arterial disease can be unrelated to atherosclerosis and caused instead by inflammation of the blood vessels (vasculitis) and old injuries that damaged blood vessels.