Anticoagulation management issues following mechanical cardiac valve replacement revolve around target levels for chronic oral anticoagulation. While these levels are important, they are only one aspect of a follow-up process that should be individualized to each patient with a mechanical cardiac valve and coupled with patient education, risk factor modification, and long-term follow-up. It is difficult to separate patient related risk factors, those traditional risk factors that markedly increase the incidence of potential valve related events (i.e., atrial fibrillation), and yet other more subtle non-traditional risk factors for thromboembolism (i.e., smoking and hypertension) that contribute to events. These also require management during the post-operative period and long-term follow-up. There are also different risk factors for anatomic valve position. The aortic valve is the safest of all the anatomic positions regarding valve related events. The mitral valve is at higher risk and the tricuspid valve is the most risky anatomic position. Anticoagulation related hemorrhage is the most dangerous event for mortality and morbidity in the aortic position, thromboembolism in the mitral position, and valve thrombosis in the tricuspid position. Each of these requires different degrees of patient modification and target levels for anticoagulation. Additionally, low risk patients with aortic valve replacement may not require anticoagulant therapy at all. Rather, treatment with modern, highly potent platelet inhibiting drugs may be effective after a period of sewing ring endothelialization under the protection of antithrombotic therapy. Each of these aspects and risk factors is discussed, as well as the call for prospective randomized trials treating low risk patients with anti-platelet drugs versus warfarin anticoagulation.