Fondaparinux is a novel antithrombotic agent, which has a number of properties that distinguish it from existing therapies (LMWHs and unfractionated heparin) for the prophylaxis and treatment of VTE. • Fondaparinux is the first in a new class of selective factor Xa inhibitors, with a unique mode of action. • Fondaparinux is an entirely synthetic, single-chemical entity, not derived from animal sources. • Fondaparinux has a pharmacokinetic profile that makes it suitable for once-daily dosing with no need for monitoring; it has no pharmacokinetic interactions with warfarin, aspirin, digoxin or NSAIDs. • The tolerability profile of subcutaneous fondaparinux 2.5 mg is not significantly different from that of the LMWH enoxaparin, with no increase in the incidence of clinically relevant bleeding episodes. • Four Phase III studies - Ephesus, Pentathlon 2000, Pentamaks and Penthifra - have demonstrated fondaparinux to be significantly superior to enoxaparin in the prophylaxis of VTE following major orthopedic surgery (risk reduction >50%), without an increase in the risk of clinically relevant bleeding. • A Phase II trial, the Rembrandt study, has demonstrated the potential of fondaparinux in the treatment of existing VTE; further evaluations for use in this indication are underway in the Matisse DVT and PE trials.