Patients undergoing cardiac surgery often experience abnormal bleeding, due primarily to cardiopulmonary bypass (CPB)-induced activation of platelets. Sevoflurane may inhibit platelet activation, raising the possibility that administering it during CPB may reduce blood loss.Patients between 18 and 65 years old who were scheduled for cardiac surgery under CPB at our hospital were prospectively enrolled and randomized to receive intravenous anesthetics alone (control group, n = 77) or together with sevoflurane (0.5-1.0 vol/%) from an oxygenator (sevoflurane group, n = 76). The primary outcome was postoperative blood loss, the secondary outcome was postoperative need for blood products.Volume of blood loss was 48% lower in the sevoflurane group than the control group at 4 hours after surgery, and 33% lower at 12 hours after surgery. Significantly fewer patients in the sevoflurane group lost >700 mL blood within 24 hours (9 of 76 vs 28 of 77, P < 0.001). As a result, the sevoflurane group received significantly smaller volumes of packed red blood cells (1.25 ± 2.36 vs 2.23 ± 3.75 units, P = 0.011) and fresh frozen plasma (97 ± 237 vs 236 ± 344 mL, P = 0.004). Thus the sevoflurane group was at significantly lower risk of requiring complex blood products after surgery (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17-0.68, P = 0.002).Sevoflurane inhalation from an oxygenator during CPB may reduce blood loss and need for blood products after cardiac surgery.