Objective: To investigate the clinical effects of a combined ultrafiltration strategy on the surgical treatment of pediatric patients with congenital heart diseases. Design: A prospective, randomized, controlled study. Setting: A single-institution study in an affiliated hospital of a university. Participants: Sixty-five pediatric patients who underwent open heart surgery with cardiopulmonary bypass (CPB) to treat congenital heart disease were enrolled. The participants were randomized into 2 groups: conventional + modified ultrafiltration (MUF) (CM) group and prime + zero-balanced + MUF (PZM) group. Interventions: In the CM group (n = 33), conventional ultrafiltration was performed after removal of the aortic clamp, and MUF was performed after the completion of CPB. In the PZM group (n = 32), ultrafiltration was performed for the circuit prime solution, zero-balance ultrafiltration was performed after removal of the aortic clamp, and MUF was performed after the completion of CPB. Measurements and Main Results: The blood gas parameters and tumor necrosis factor alpha content in the priming solution and perioperative blood samples were analyzed. Postoperative parameters, including mechanical ventilation time, respiratory indices, intensive care unit time, and hospital time, also were recorded. One hospital death occurred in each group. No severe complications occurred in either group. The lactic acid, glucose, and tumor necrosis factor alpha contents in the priming solution and perioperative blood samples were significantly lower in the PZM group compared with the CM group. The respiratory indices were statistically significantly better in the PZM group compared with the CM group in the early postoperative period. No significant differences were found between the 2 groups regarding the postoperative ventilation time, inotropic support, homologous blood transfusion, drainage, intensive care unit time, or postoperative hospital time. Conclusion: The combined use of ultrafiltration of prime solution, zero-balance ultrafiltration, and MUF strategy is associated with a modest improvement in pulmonary function compared with the combination of conventional and MUF strategies in the early postoperative period, but the principal clinical outcomes are similar. © 2013 Elsevier Inc. All rights reserved.