This retrospective study analyzed the current practice of blood transfusion-free open-heart surgery in 536 children weighing 5-20 kg undergoing surgery between 2004 and 2007. A miniaturized cardiopulmonary bypass (CPB) circuit was used (priming volume; 300 ml for the flow rate <1,500 ml/min; 550 ml for the flow rate of 1500-2300 ml/min). Modified ultrafiltration was routinely performed. Criteria for blood transfusion during CPB included a hematocrit of <20% and/or mixed venous oxygen saturation of <65%. Transfusion during CPB was avoided in 264 (49.3%) of the 536 patients (5-10 kg group, 29.0%; 11-15 kg group, 67.4%; 16-20 kg group, 80.8%). There was no neurological complication related to hemodilution. Multiple logistic regression analysis revealed that body weight, preoperative hematocrit, priming volume of CPB circuit, CPB time, and lowest hematocrit during CPB predict requirement of blood transfusion (p < 0.01). Transfusion rate was lowest in the atrial septal defect group (5.6%) and highest in tetralogy of Fallot group (78.7%), being associated with complexity of diagnosis and procedure required. Blood transfusion-free open-heart surgery may be achieved in the half of the patients weighing 5-20 kg, and further miniaturization of CPB circuit and refinement of perfusion strategy might reduce transfusion rate in patients <10 kg and/or with complex congenital heart disease.