Over recent years, increasing awareness has been aroused to the hazards of the utilization of donor blood products. Particularly in neonate cardiac surgery employing cardiopulmonary bypass (CPB), the relative high priming volume of the CPB system and its adjunctive components, such as hemofilters, causes severe hemodilution and, therefore, particularly during extended perfusions, customarily requires priming of the system with autologous blood components. We report on our efforts to minimize the CPB system and adjust the perfusion strategy to the goal of transfusion-free CPB in a 3.7 kg neonate scheduled for repair of transposition of the great arteries.