Pharmacological adjuvant therapies to protect against procedure-related thrombotic complication are indispensable during percutaneous coronary intervention. In addition to antiplatelet therapy, use of anticoagulants to prevent acute thrombotic complication during percutaneous coronary intervention is essential. Besides unfractionated heparin (UFH), new anticoagulants have been developed and compared with UFH. Low-molecular weight heparins, direct thrombin inhibitors (e.g. bivalirudin), and recently developed agents such as fondaparinux (a factor Xa inhibitor) provide new alternatives to conventional UFH.