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Venous graft disease is a thromboproliferative process and places a serious limitation on the symptom-free survival of patients after coronary artery bypass grafting. The efficacy of antithrombotics, especially during the first year after surgery, is suggested by an understanding of the four described phases of disease development. Studies examining the usefulness of hemostatic factors, such as lipoprotein (a) and fibrinogen, in identifying patients at added risk for graft occlusion are reviewed. Aspirin begun within the first day after surgery remains the mainstay of current preventive therapy, but the potential for other antiplatelet agents alone or in combination is explored. In a two-by-two trial, the efficacy of low-dose oral anticoagulation with warfarin (Coumadin) was equivocal. Aggressive cholesterol reduction decreased progression and need for revascularization by 30%. Future examinations are needed to define the optimal intensity and timing of therapy and to explore the role of newer, more potent antithrombotic agents.