Over the last 5 years, new oral anticoagulant options, including dabigatran, rivaroxaban and apixaban, have become available. Prior to this, vitamin K antagonists were the sole oral anticoagulants, which have been in use for more than 60 years. These novel agents have been studied in a variety of patient populations, including atrial fibrillation, acute coronary syndrome, treatment of venous thromboembolism and thromboprophylaxis. Compared with standard care, these agents have largely been found to be noninferior or superior for efficacy end points, with similar or improved rates of bleeding. As a result, these agents have become attractive alternatives to vitamin K antagonists for the prevention and treatment of thromboembolic disease. This article provides a summary of clinical trial data to help clinicians determine which agent is most appropriate for a given patient.