Background and rationale for the study (Efficacy and toxicity of warfarin): Warfarin reduces the risk of first or recurrent venous thrombosis by 80 to 90 percent, and reduces the risk of first or recurrent arterial thrombosis by 50 to 65 percent (1;2). In North America more than 1 million patients receive warfarin on a daily basis and in Ontario more than 300,000 prescriptions for warfarin are filled annually. The major toxicity of warfarin is bleeding, which may be fatal. Although bleeding may occur when the international normalized ratio (INR) is in the "therapeutic range" (2.0 to 3.0 for most indications), many patients who bleed have supratherapeutic INR values. Indeed, large studies suggest patients spend 10 to 20 percent of their time with excessively prolonged INR values and one anticoagulation clinic has reported that out of 7,279 patients managed over a 5 year interval, 1,995 had at least one INR greater than 6.0 (3). Furthermore, the risk of hemorrhage approximately doubles for each increase in the INR of 1.0 unit (4-7).