Oral anticoagulant therapy is used extensively in the treatment of deep venous thrombosis-pulmonary embolism and prevention of systemic thromboembolism. Adoption of the International Normalized Ratio system for the laboratory monitoring of therapy has solved the problems encountered with the variable sensitivities of the available thromboplastins in North America. Although in recent years the recommended intensity of treatment has been reduced for many indications, bleeding remains the most common side effect of long-term oral anticoagulation therapy. Several drugs interact with warfarin sodium, the most commonly used oral anticoagulant drug, and potentiate its effect, thereby increasing the risk of bleeding. However, awareness of potential drug interactions and careful monitoring to maintain patients within the recommended therapeutic ranges can minimize the risk of bleeding and lead to its safe use in most patients.