Purpose: A recent study analyzing several cytokines reported that long cardiopulmonary bypass (CPB) time and long aortic cross clamp (ACC) time were accompanied by enhanced postoperative inflammation, which contrasted with the modest influence of the degree of hypothermia. In this present study, we aimed to examine the effect of CPB temperature on the clinical outcome in infants undergoing repair of isolated ventricular septal defect (VSD). Methods: Of the 212 infants with isolated VSD who underwent open heart surgery (OHS) between January 2001 and December 2010, 43 infants were enrolled. They were classified into 2 groups: group 1, infants undergoing hypothermic CPB ($26^{circ}C-28^{circ}C$; n=19) and group 2, infants undergoing near-normothermic CPB ($34^{circ}C-36^{circ}C$; n=24). Results: The age at the time of the OHS, and number of infants aged<3 months showed no significant differences between the groups. The CPB time and ACC time in group 1 were longer than those in group 2 (88 minutes vs. 59 minutes, P =0.002, and 54 minutes vs. 37 minutes, P =0.006 respectively). The duration of postoperative mechanical ventilation was 1.6 days in group 1 and 1.8 days in group 2. None of the infants showed postoperative neurological and developmental abnormalities. Moreover, no postoperative differences in the white blood cell count and C-reactive protein levels were noted between two groups. Conclusion: This study revealed that hypothermic and near-normothermic CPB were associated with similar clinical outcomes and inflammatory reactions in neonates and infants treated for simple congenital heart disease.