Antithrombotic therapy is essential for secondary stroke prevention. Clinical practice guidelines recommend anticoagulant and antiplatelet drug administration as first-line therapy for cardioembolic stroke and non-cardioembolic infarction, respectively. Direct oral anticoagulants represent first-choice treatment for cardioembolism secondary to non-valvular atrial fibrillation owing to few hemorrhagic complications associated with this therapy. However, warfarin with optimal control of the international normalized ratio for standardization of prothrombin time is preferred in patients with kidney dysfunction, artificial valve implantation, valvular heart disease, and cardiomyopathy. Antiplatelet drugs, including aspirin, clopidogrel, and cilostazol are used in patients with non-cardioembolic infarction. Dual antiplatelet agents, including aspirin and clopidogrel, are recommended during the acute stage because of the high risk of recurrent ischemic stroke. In contrast, a single antiplatelet drug is recommended during the chronic stage to avoid the risk of intracranial hemorrhage.