Peri-operative transfusion of blood or blood products is associated with increased morbidity and mortality after cardiac surgery. However, excessive hemodilution as a result of avoiding the use of homologous blood products can also lead to decreased oxygen delivery to vital end organs and dilutional coagulopathy. This is particularly challenging in pediatric cardiac surgery where there is a large discrepancy between the patient circulating blood volume and the priming volume of the cardiopulmonary bypass (CPB) circuit. Strategies to avoid the use of homologous blood products during pediatric cardiac surgery must also incorporate miniaturization of the CPB circuit and other bypass techniques in order to avoid problems with excessive hemodilution. We report a 5.9 kg male infant who underwent successful surgical correction of a ventricular septal defect without the use of homologous blood transfusion. Our strategies included the pre-operative administration of erythropoietin and iron to increase red blood cell mass, acute normovolemic hemodilution (ANH) before the institution of CPB, retrograde autologous priming (RAP), cell salvage, continuous ultrafiltration, vacuum-assisted venous drainage to minimize the circuit size and priming volume, and the use of near infrared spectroscopy (NIRS) to monitor the patient during the entire procedure. The utilization of these strategies is now standard for our entire pediatric cardiac surgical population.