Recent years have shown a diverse array of new antithrombotic drugs in development or appearing in clinical practice. Until now, warfarin has remained the anticoagulant drug of choice despite the numerous disadvantages associated with its use. Ximelagatran, an oral direct thrombin inhibitor (DTI), has now emerged as a serious contender to replace warfarin as standard anticoagulation. Its use in prophylaxis and treatment of venous thromboembolic disease is already well established and recent data also suggest the benefits of ximelagatran over warfarin in non-valvular atrial fibrillation, both in terms of safety and efficacy. This review will examine ximelagatran as a novel anticoagulant with its application in numerous clinical settings, such as venous thromboembolism and non-valvular atrial fibrillation, and how it may one day replace warfarin as the anticoagulant of choice.