Venous thromboembolism (VTE) involves the formation of a thrombus in the venous vasculature, manifesting as deep vein thrombosis or pulmonary embolism. Anticoagulants are effective antagonists of coagulation and are typically prescribed to patients to prevent VTE. The goal of this chapter is to outline the use of antiplatelet drugs to combat VTE. Compared to traditional anticoagulants, antiplatelet drugs are associated with a reduced risk of bleeding, making them particularly relevant for frail patients with an elevated VTE risk, such as those undergoing orthopaedic surgery, trauma patients, individuals with cancer, or hospitalized patients. Clinical trials have shown that antiplatelet therapy, particularly aspirin, may benefit select patient populations with a relatively low risk of VTE while high-risk VTE populations should commit to anticoagulants. Current guidelines do not recommend antiplatelet agents for the prevention of recurrent VTE. Despite their limited use in current clinical practice, preclinical studies targeting novel platelet pathways suggest the potential for developing novel therapies that prevent VTE while minimizing bleeding risk, warranting further clinical investigation.