Thrombosis and bleeding are among the most common causes of morbidity and mortality in patients with renal disease or liver disease. The pathophysiology underlying the increased risk for venous thromboembolism and bleeding in these 2 populations is distinct, as are considerations for anticoagulation. Anticoagulation in patients with kidney or liver disease increases the risk of bleeding; this risk is correlated with the degree of impairment of anticoagulant elimination by the kidneys and/or liver. Despite being in the same pharmacologic category, anticoagulant agents may have varied degrees of renal and liver metabolism. Therefore, specific anticoagulants may require dose reductions or be contraindicated in renal impairment and liver disease, whereas other drugs in the same class may not be subject to such restrictions. To minimize the risk of bleeding, while ensuring an adequate therapeutic effect, both appropriate anticoagulant drug choices and dose reductions are necessary. Renal and hepatic function may fluctuate, further complicating anticoagulation in these high-risk patient groups.