For decades, the standards of antithrombotic therapy have been heparin and coumarin compounds, primarily warfarin (1). Other newer approaches include low-molecular-weight heparins, fondaparinux, lepirudin, argatroban, and melagatran (investigational). Although existing treatments are effective, they have many limitations. A safer, more convenient therapy is needed. Ximelagatran is the first oral treatment in a new World Health Organization class of direct thrombin inhibitors and is the first new oral anticoagulant since the introduction of warfarin almost 60 years ago (2). It was submitted to the Food and Drug Administration (FDA) for approval in December 2003 (3). Each year, nearly 4 million people worldwide experience a primary thrombotic event, and those at greatest risk include people with atrial fibrillation, those who have experienced a previous cardiac event such as a myocardial infarction, and patients who have recently undergone orthopaedic surgery, such as total hip or knee replacement surgery (4). Current mainstays of therapy for preventing or treating thrombosis are not ideal. Warfarin, although available in an oral form, has a slow onset of action, interacts with numerous foods and drugs, and requires intensive monitoring of coagulation with frequent dose adjustments. Heparins, fondaparinux, lepirudin, argatroban, and melagatran (investigational) are limited by their route of administration, especially in an outpatient setting, as all are administered parenterally (5, 6). Ximelagatran, a prodrug of melagatran, is an orally administered direct inhibitor of both free and clot-bound thrombin. It is rapidly absorbed and quickly converted to its active form, melagatran, with stable and reproducible pharmacokinetic properties. No clinically significant interactions with food or cytochrome P450-metabolized drugs have been reported for ximelagatran, and the drug requires no monitoring (7).