Objective: In neonatal and infant cardiac surgery with cardiopulmonary bypass (CPB), hemodilution with reduction of plasma albumin concentration and low colloid oncotic pressure (COP) are the main factors associated with tissue edema and postoperative weight gain. The aim of our study was to evaluate the influence of two different COP regulatory strategies on post-bypass body weight gain, fluid balance, and clinical outcomes. Methods: Seventy elective patients with body weight < 10 kg underwent first-time cardiac surgery with CPB and were randomized into two groups. The standard COP group received 0.5 g kg(-1) of human albumin in the priming and, during CPB, albumin was added to maintain the COP > 15 mmHg. In the high COP group, albumin concentration in the priming was 5% and, during CPB, the COP was maintained above 18 mmHg. All patients were monitored before, during and until 24 h postoperatively. Data were collected on body weight gain, COP, albumin concentration, fluids transfusion, blood loss, urine production and laboratory results. Results: Patients' demographics and operative data were comparable. Although the high COP group had perioperatively significantly higher COP and albumin concentration than the standard COP group, no significant difference was found in the body weight gain. There were also no significant differences between the groups with respect to fluid balance, urine output and blood loss. However, the high COP group had significantly shorter postoperative duration of mechanical ventilation (10 h vs 14 h, p = 0.02) and lower plasma lactate concentration post operation (1.1 mmol l(-1) vs 1.4 mmol l(-1), p = 0.046). Conclusions: The COP regulatory strategy for neonatal and infant CPB, based upon the 5% concentration of albumin in the priming and a COP target of 18 mmHg during bypass, better preserves the plasma albumin concentration within the physiological range and stabilizes the colloid pressure than the standard strategy (0.5 g kg(-1) albumin in the priming and bypass COP target at 15 mmHg). Nevertheless, only the lower postoperative plasma lactate concentration and the shorter duration of mechanical ventilation in the high COP group indicated the potential clinical benefit of this new strategy. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.