We studied the effect of known concentrations of heparin on the prothrombin time (PT) in patients receiving warfarin and in controls who were not anticoagulated. Plasma from the subjects and controls was serially diluted with known concentrations of heparin, and PT was measured. Linear regression of heparin concentration versus percentage change in PT resulted in r=0.86 in the warfarin group and r=0.72 in the control group. The warfarin group was more sensitive to the effects of heparin than the control group, as manifested by a steeper slope of the regression line (p<0.001). Over the therapeutic range of heparin concentration (0.2‐0.4 units/ml), the 95% prediction interval of the percentage change in PT was −6–12% at 0.2 units/ml, and 2–20% at 0.4 units/ml in the warfarin group. These results demonstrate a strong relationship between the heparin concentration in plasma and the percentage change in the PT. This effect should be considered when adding warfarin to the regime of patients receiving heparin therapy.