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At present, unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) are used extensively for the prophylaxis and treatment of venous thromboembolism (VTE) and in most cases represent the agents of choice for these indications. However, both UFH and LMWHs have biophysical limitations. Over the past years, the progress in molecular biology and biotechnology has stimulated growing interest in hirudin, the most potent known natural inhibitor of thrombin. The biological properties of hirudin combined with its ready availability as recombinant forms make this drug well-suited for use as an anticoagulant agent. Available studies indicate that hirudin is significantly more effective for prophylaxis of VTE after total hip replacement than is either UFH or enoxaparin. Only limited data are available on its efficacy in the treatment of deep vein thrombosis. Moreover, hirudin is effective in the management of patients with heparin-induced thrombocytopenia (HIT) who require further anticoagulation. In conclusion, hirudin is an antithrombotic drug of high quality and may represent an attractive alternative to UFH and LMWHs in the management of VTE, and it is among the agents of choice in patients with contraindications to heparin therapy (such as HIT patients).