In the present review, the role of oral anticoagulants (OAC) in the secondary prophylaxis a long term after myocardial infarction (MI) is discussed in the light of the results from recently published large randomized controlled trials (RCTs). In particular, comparision with aspirin, alone or in combination with OAC, is presented. The pathophysiological role of atherothrombosis in MI, with special stress on the crucial role of thrombin generation representing a special rationale for OAC prophylaxis, is emphasized. Recent RCTs clearly show the superiority of OAC over aspirin to reduce clinical end points a long term after MI. A prerequisite for optimal effect of OAC is a knowledge of the narrow therapeutic window towards bleeding complications. This necessitates good patient compliance and strict control of the treatment. The INR threshold for effective prophylaxis with OAC after MI, when given alone or in combination with aspirin, is also presented. The possibility of self-management of INR controls with satisfactory quality and cost reduction is also highlighted. Finally, the combination of OAC with a target INR of 2.0-2.5 (2.3) and aspirin of 75 mg/day is especially recommended.