The concentrations of two antibiotics (vancomycin and cefuroxime) in sternal bone during coronary artery bypass surgery were analyzed to examine whether antibiotic penetration is impaired after dissection and harvesting of the left internal mammary artery for grafting. Bone samples (250 mg of cancellous sternal bone from both halves of the dissected manubrium) were obtained at the time of sternal opening and closure. Twenty patients undergoing primary coronary artery bypass grafting with the left internal mammary artery were randomized so that ten received 1.5 g of vancomycin over 180 minutes and ten 3 g of cefuroxime over 30 minutes beginning at the time of induction of anesthesia. Serum samples were collected at the same time as the bone samples and 12 h after the start of the infusions. There was a slight difference in vancomycin concentration between two sternal halves after IMA dissection at the time of sternal closure (median difference, 0.2 µg/g, and 95% confidence interval, -0.55 to 0.1). This difference was not statistically significant at the P = 0.05 level (P = 0.15, Wilcoxon matched-pair test). The cefuroxime concentration of the bone was below the detection limit (7.6 to 9.2 µg/g) in all ten patients at the time of sternal closure. Harvesting the internal mammary artery for coronary artery bypass grafting may influence the concentration of vancomycin in the manubrium of the sternum.