Single antiplatelet therapy with aspirin or clopidogrel is widely used in the prevention of adverse cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD). However, the risk of these events remains high, and the most optimal antithrombotic therapy for PAD is still uncertain. We conducted a literature search to identify themajor clinical trials on therapeutic approaches in the prevention of adverse events in patients with PAD. This article provides an overview of the clinical trials that have evaluated the efficacy and safety of intensified antithrombotic strategies for PAD. Due to the heterogeneity of patient populations and the variable definitions of clinical outcomes used in different clinical studies, it was difficult to make direct comparisons between the study results. Although a number of choices are nowavailable, the risk-benefit of each antithrombotic regimen for patients with PAD must be carefully considered.