Objective: To investigate impact of prophylactic peritoneal dialysis (PD) on clinical outcomes and inflammatory cytokines in children following cardiac surgery with cardiopulmonary bypass. Design: Prospective before-and-after nonrandomized cohort study. Setting: Pediatric cardiovascular intensive care unit in tertiary hospital. Patients: Fifty-two consecutive neonates and infants at high risk for postoperative fluid overload following cardiopulmonary bypass. All had PD catheters placed during primary cardiac surgery. Intervention: Initial 27 patients were managed with passive peritoneal drainage and diuretics (controls). Following 25 patients were started on prophylactic PD in immediate postoperative period and managed per PD protocol (+PD). Outcome Measures: Cumulative fluid balance, indices of disease severity, and clinical outcomes were prospectively collected. Plasma interleukin-6 and interleukin-8 were measured immediately before-and-after cardiopulmonary bypass and at 24 and 48 hours post-cardiopulmonary bypass. Results: Demographics, diagnoses, and intraoperative variables were similar. Median net fluid balance was more negative in +PD at 24 hours, -24mL/kg (interquartile range: -62, 11) vs. +18mL/kg (interquartile range: -26, 11), P =.003, and 48 hours, -88mL/kg (interquartile range: -132, -54) vs. -46mL/kg (interquartile range: -84, -12), P =.004. +PD had median 55mL/kg less fluid intake at 24 hours, P =.058. Peritoneal drain, urine, and chest tube output were comparable over first 24 hours. Mean inotrope score was lower in +PD at 24 hours. +PD had earlier sternal closure-24 hours (interquartile range: 20, 40) vs. 63 hours (interquartile range: 44, 72), P <.001-and a trend toward shorter duration of mechanical ventilation-71 hours (interquartile range: 49, 135) vs. 125 hours (interquartile range: 70, 195), P =.10. +PD experienced lower serum concentrations of interleukin-6 and interleukin-8 at 24 hours. Conclusions: Prophylactic PD is associated with greater net negative fluid balance, decreased inotrope requirements, and lower serum concentrations of inflammatory cytokines in the early postoperative period. © 2013 Wiley Periodicals, Inc.