The response to initiation of oral anticoagulants at a usual dose of 5 mg of warfarin has been retrospectively evaluated in patients following heart valve replacement (HVR). Patients starting oral anticoagulants after HVR have a lower target International Normalized Ratio (INR) (1.5 to 2.6) until the pacing wires are removed after operation. The mean daily doses and INR responses after HVR and nonsurgical patients were retrospectively compared during the first 5 days of warfarin treatment. In a subset from both groups, the mean dose of warfarin was correlated with age, body weight, and albumin levels. Eighty-four HVR and 32 nonsurgical patients were studied. The mean daily warfarin dosage was 3.29 ± 1.29 mg after HVR and 4.96 ±1.76 mg in controls (p <0.001), and the mean INRs 2.08 ± 0.60 and 1.60 ± 0.54, respectively (p <0.001). Of the HVR patients and controls, 48.8% and 21.8%, respectively, exceeded the upper level of the targeted range (p = 0.014), 86.9% and 40.6% had the dose reduced after the first 5 mg (p <0.001), and 54.7% and 28.1%, respectively, had warfarin withheld for at least 1 day (p = 0.015). Thirty-nine patients were included in the subset analysis. Patients with serum albumin levels <35 g/L required significantly less warfarin (3.84 mg/day) than patients with levels ≥35 g/L (5.37 mg/day; p <0.05). Thus, patients starting oral anticoagulation after HVR are significantly more sensitive to warfarin than nonsurgical patients. Patients with serum albumin levels below the normal values require less warfarin than patients with normal values during the initial phase of treatment.