Vitamin K antagonists (VKAs) are used to prevent and treat venous thromboembolism and to prevent arterial thromboembolism in patients with atrial fibrillation or cardiac disease, including mechanical heart valves. The International Normalized Ratio (INR) is commonly used to monitor the effect of VKA therapy. In contrast to heparin, which has an almost immediate effect, VKAs have a delayed onset because it takes time for the already synthesized coagulation factors to be cleared from the circulation. Indications for VKA therapy include many diseases and conditions, such as primary prevention of venous thrombosis, treatment of deep vein thrombosis and/or pulmonary embolism, prevention of recurrent thromboembolism, heart valve replacement and heart valve diseases, atrial fibrillation, before and after cardioversion, dilated cardiomyopathy, and some rare diseases, including antiphospholipid syndrome, congenital thrombophilia, and paroxysmal nocturnal hemoglobinuria. Combined antiplatelet and anticoagulant therapy may also be considered, especially in patients at high risk of venous and arterial thromboembolic events.