Thrombin plays a key role in the pathogenesis of acute coronary syndromes because it is a potent platelet agonist and converts fibrinogen to fibrin. Hirudin is a powerful, direct, and specific antithrombin agent that can be used in many therapeutic scenarios in which heparin is routinely used. In this systemic review, we summarize evidence from randomized clinical trials evaluating the benefits and risks of recombinant hirudin for the treatment of acute coronary syndromes and patients undergoing percutaneous coronary intervention.