Thromboembolic and ischemic complications frequently occur during and after endovascular procedures, because of associated arterial injury and the thrombogenic characteristics of arterial catheters, contrast agents, and implanted devices such as coils and stents. Platelet adhesion, activation, and aggregation occurring at the site of arterial injury are mediated by local factors, including thromboxane A2 (inhibited by aspirin) and adenosine diphosphate (inhibited by ticlopidine and clopidogrel). Concomitantly, thrombin is formed by serial activation of clotting factors via contact with subendothelial tissue factor. Thrombin cleaves fibrinogen into fibrin. Thrombin activation is indirectly blocked by heparin and its analogs. However, after thrombin is clot-bound (with fibrin), it is relatively protected from heparin and is effectively blocked only by direct thrombin inhibitors (hirudin and its analogs). The final common pathway in clot formation is the binding of fibrinogen to platelets via platelet glycoprotein IIb/IIIa receptors, which is inhibited by antibodies to platelet IIb/IIIa receptors. New treatment modalities, such as the use of direct thrombin inhibitors and antibodies to platelet glycoprotein IIb/IIIa, seem to be more effective for prophylaxis and treatment than conventional anticoagulation and antiplatelet therapies.