Endothelial dysfunction takes a relevant part in the pathophysiology of IC, with 2/3 of the patients showing an EF lower than the pathological cut-off. Maximal exercise worsens the EF, according to the trend associated with the acute inflammatory response. All these features suggest that physical activity in IC should not utilize the maximal working load, in order to avoid the high inflammatory activation and the acute complications of atherosclerotic plaque. The supervised physical training, besides confirming itself as the most effective means to increase the walking ability, also proved to be able to improve the EF of these patients, as described about other diseases. It is probable that moderate hemodynamic stress reduces the levels of the inflammatory markers and increases the flow-mediated vasodilation through an ischemic preconditioning. The increased walking ability, associated with the improvement of EF could improve the heavy systemic outcome of claudicant patients, as it has been demonstrated in patients with coronary heart disease. Further prospective survival studies on cardiovascular outcomes of trained claudicant patients are needed.