Fondaparinux (Arixtra®; Sanofi-Synthélabo/Organon) is the first of a new class of antithrombotic agents distinct from low molecular weight (LMW) heparins and heparin. It is a synthetic pentasaccharide mimicking the site of heparin that binds to antithrombin III (AT). It is homogeneous with a molecular weight of 1728 Da. It exhibits only factor (F) Xa inhibitor activity via binding to AT, which in turn inhibits thrombin generation. It does not inhibit thrombin, release TFPI, or possess other actions of heparin. Low AT levels can limit the efficacy of fondaparinux. There is nearly complete bioavailability subcutaneously, rapid onset of action, a prolonged half-life (15- 20 h) and no metabolism preceding renal excretion. Elderly and renal impaired patients have reduced clearance. The PT, aPTT and ACT are not affected by fondaparinux; anti-FXa assays are used if needed. Phase IIb clinical studies have identified a fixed dose of 2.5 mg once daily for prophylaxis of venous thrombosis without monitoring. Four phase III studies (n > 7000) demonstrated a combined 55% relative risk reduction of venous thromboembolic events in orthopedic surgery patients in comparison to the LMW heparin enoxaparin. Hemorrhagic complications for fondaparinux were either comparable to or higher than that for LMW heparin. The US FDA and the European CPMP have approved fondaparinux for prophylaxis of venous thrombosis after orthopedic surgery with limitations of use in elderly, low weight, renal impaired patients and in those receiving spinal anesthesia. Marketing is expected in Spring 2002. Clinical trials for treatment of established thrombosis, coronary syndromes and adjunct to thrombolytic therapy are in progress.