We evaluated the efficacy of the extended use of hemofiltration (EHF) and high perfusion flow rate in cardiopulmonary bypass (CPB) in pediatric open-heart surgery retrospectively. In the EHF method, hemofiltration was used for hemic prime before initiation of the bypass and ultrafiltration was used throughout the bypass. Thirty-four children, with transposition of great arteries who were undergoing arterial switch operation with the use of hemic prime, were subjects of this study. They were divided into 2 groups, a control group (n = 16) and a group (n = 18) that underwent EHF. There were no significant differences between groups in demographics, but the maximum perfusion index and lowest rectal temperature were higher in the EHF group. This study compared urination during bypass, arterial oxygen pressure at the end of bypass and operation, the duration of the ventilation, and postoperative soft tissue index (STI) expressing the severity of edema. In the EHF group, urination during bypass was significantly higher, and there was a tendency to higher arterial oxygen pressure. The patients in the EHF group were weaned from the ventilator significantly earlier. Postoperative STI was significantly higher, so edema was more severe in the control group. We consider that the use of EHF and a high perfusion flow rate in CPB are an ideal method to improve the perioperative fluid balance in pediatric open-heart surgery. We suspect that these good clinical effects result from maintaining the inflammatory mediators at a low level throughout the bypass, reducing the following release of the mediators and attenuating the interaction of the mediators.