Acute coronary syndrome (ACS) is a leading cause of mortality worldwide. Despite optimal antiplatelet therapy recommendation after ischemic events, recurrent thrombotic complications rate remains high. The recurrent events maybe in part due to increased thrombin levels during ACS which may underscore the need for an additional anticoagulation therapy. Given the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) over warfarin, they have the potential to prevent thrombus formation, in the presence or absence of atrial fibrillation, but at the cost of increased risk of bleeding. NOACs have also shown a promising efficacy in managing left ventricular thrombus and a potential benefit in avoiding stent thrombosis after percutaneous coronary revascularization. Taken as a whole, NOACs are increasingly used for off-licence indications, and continue to evolve as essential therapy in preventing and treating thrombotic events. Herein, this review discusses NOACs off-label indications in the setting of ischemic coronary disease.