Oral anticoagulation (OA) has been used to treat patients with coronary artery disease (CAD) for more than 40 years and has been a subject of intense controversy since that time. Seven to 10% of patients with acute myocardial infarction (MI) develop recurrent MI, stroke, or death in the 6 weeks following the index event and approximately 20% after 4 years, despite optimal background therapy with aspirin. Recent large studies and systematic reviews have greatly clarified the role of OA in the modern era. On the weight of the evidence, which is reviewed in detail in this article, long-term, moderate-intensity OA (International Normalized Ratio 2.0 to 3.0) should be considered an option for the prevention of recurrent CAD, particularly in high-risk patients.