Atherosclerotic cardiovascular disease (ASCVD), particularly myocardial infarction (MI), is the leading cause of mortality and morbidity worldwide. The pathophysiology of MI involves atherosclerotic plaque rupture with thrombus formation, interrupting myocardial blood supply with subsequent myocardial necrosis. Despite advances in primary prevention and acute revascularization strategies for MI, recurrent ischemic events and stent thrombosis continue to pose challenging issues for clinicians. Consequently, effective secondary prevention, specifically antiplatelet therapy (aspirin and P2Y12 inhibitors), is the cornerstone of the prevention of recurrent ischemia and cardiovascular death to improve long-term prognosis. However, the optimal choice and duration of antiplatelet therapy should be individualized depending on risk factors and comorbidities. This review will explore the mechanisms of thrombosis in MI, the role of antiplatelet therapy in secondary prevention after MI, and the clinical evidence supporting various antiplatelet agents, focusing on their pharmacological profiles, efficacy, safety considerations, guideline recommendations, and application in special populations based on available clinical trial data while highlighting key controversies, knowledge gaps, and emerging strategies such as biomarker-guided and genotype-guided therapy.