Background: The use of blood products is often necessary to prime the extracorporeal circuits for pediatric cardiac surgical patients. The use of blood products carries serious risks both in the acute and long-term aspects of patient care. However, excessive hemodilution during cardiopulmonary bypass (CPB) is associated with decreased oxygen carrying capacity, edema, and organ dysfunction. Especially, whether brain dysfunction after transfusion-free cardiac surgery on CPB occurred is unknown. Objective: This study aims to investigate whether excessive hemodilution affects child’s mental development. Methods: We studied 143 infants (24.2 +/− 15.8 months, 5 months ~ 3 years of age) had performed surgical closure of ventricular septal defect (VSD) in less than 12 months (4.8 +/− 2.6 months) of age in 7 children’s hospitals. Questionnaires mailed to the parents included the Tsumori-Inage Infant Developmental Scale estimating subjects’ behavioral developmental level as Developmental Quotients (DQ). The infants were divided into 3 groups; transfusion-free (Group A, n=52), transfusion during CPB (Group B, n=24) and transfusion after CPB (Group C, n=66). Results: Lower DQ was found for Group A (94.7 +/− 11.6) than Group B (103.5 +/− 16.0, p=0.008) and Group C (101.7 +/− 17.9, p=0.016). No correlation was found between DQ and minimum hemoglobin level during CPB (min-Hb) in Group A. The DQ was likely to be lower in the infants with below 6 g/dl (93.0 +/− 13.0) than with over 6 g/dl (98.7 +/− 8.3. p=0.10) of min-Hb. Conclusions: The results suggest that the infants after transfusion-free surgery of VSD on CPB delay in the mental development in their early childhood. Maintaining minimum hemoglobin level over 6 g/dl during CPB seems to prevent the mental development from delay.