The occurrence of disabling stroke, the major fatal consequence of atrial fibrillation, can be reduced by almost two-thirds with warfarin oral anticoagulation. Recent estimates on the prevalence of atrial fibrillation in the USA suggest that approximately 3 million people suffer from this common cardiac arrhythmia, therefore, the socioeconomic impact of adequate oral anticoagulation is enormous. Rivaroxaban, a direct orally available factor Xa inhibitor, is the first of a new class of drugs that target a central factor of the coagulation cascade upstream of thrombin. In the ROCKET AF clinical trial, rivaroxaban demonstrated noninferiority compared with warfarin for stroke prevention in patients with atrial fibrillation, while intracranial and fatal bleeding occurred less frequently with rivaroxaban treatment. Rivaroxban has recently been approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation by the US FDA and EMA. Very recently, rivaroxaban in addition to dual antiplatelet therapy, was shown to reduce mortality in patients with a recent acute coronary syndrome in the ATLAS ACS 2-TIMI 51 clinical trial. The clinical evaluation of rivaroxaban in cardiovascular disease and the results of the ROCKET AF study, the landmark clinical trial of rivaroxaban for stroke prevention, are discussed along with the unique pharmacological profile of rivaroxaban.