eripheral artery disease (PAD) is a term that relates to atherosclerosis and narrowing of the arteries in the lower extremities. The prevalence of PAD is approximately 12% of the adult population. Despite the low rate of peripheral complications and amputation, PAD is complicated by a high rate of cardiovascular events including myocardial infarction, stroke, and vascular death with an annual incidence of about 5%. The detection of PAD is initially based on the appearance of typical symptoms (claudication and critical limb ischemia) related to peripheral arterial insufficiency. However, PAD may also be present in the absence of clinical symptoms (asymptomatic PAD). Accordingly, asymptomatic disease may occur in up to 50% of all patients with PAD. Ankle brachial index (ABI) is a diagnostic test used to evaluate the presence of PAD, defined by an ABI ≤0.90. The ABI is also demonstrated to be useful in the assessment of vascular risk in asymptomatic and symptomatic patients. Antiplatelet therapy remains a key intervention to reduce cardiovascular risk in PAD. Data from Antithrombotic Trialists’ Collaboration showed that antiplatelet treatment was associated with a 23% risk reduction of vascular events in overall population with PAD. However, closer scrutiny of these data reveals that nonaspirin antiplatelet drugs, including ticlopidine, clopidogrel, picotamide, and dipyridamole largely drove the benefits in the PAD subgroup. It remains an open issue if PAD represents an atherosclerotic clinical model where aspirin, differently from coronary heart disease, is less effective in reducing atherosclerotic progression. Based on the reported results further trials with aspirin should be done in asymptomatic (ABI ≤0.90) and symptomatic PAD patients. Finally, the role of new antiplatelet drugs such as prasugrel and ticagrelor has not yet been studied in PAD.