Warfarin currently is the most widely used agent in the prevention of thrombosis and embolism after prosthetic cardiac valve replacement. Since smoking has been shown to increase the requirement for medications undergoing hepatic metabolism, this study was designed to determine if a correlation exists between smoking history and warfarin daily maintenance dose (DMD) in patients undergoing cardiac valve replacement. Of 200 charts retrospectively reviewed at the New England Medical Center, 174 satisfied the criteria for inclusion in the study (normal hepatic, renal, and hematologic function, and absence of complicating medications). The study population included aortic, mitral, and combined valve replacement. Study groups consisted of 117 nonsmokers (Group A), 23 light smokers (Group B), and 34 heavy smokers (Group C). Thirty-three percent of patients required a low DMD of warfarin (less than or equal to 2.5 mg), 43 percent required a moderate DMD (greater than 2.5-7.5 mg), and 24 percent required a high DMD (greater than 7.5 mg). Each of the subgroups followed a similar pattern. In Group A, there were 31 percent low, 44 percent moderate, and 25 percent high-dose requiring patients. In Group B, there were 48 percent low, 39 percent moderate, and 13 percent high-dose requiring patients and in Group C there were 29.5 percent low, 41 percent moderate, and 29.5 percent high-dose requiring patients. Chi-square analysis did not demonstrate any statistically significant difference between smokers and nonsmokers in regard to daily maintenance warfarin dose (p = 0.5). The study population followed a normal pattern of distribution in regard to warfarin dosage. On the basis of these data we conclude that smoking history does not affect warfarin dose requirement.