The contact of blood with nonbiological surfaces during cardiopulmonary bypass (CPB) induces a whole body inflammatory response and increases postoperative morbidity directly related to bleeding complications and end organ dysfunction. Methods to reduce these effects have included modification of extracorporeal circuits through biocompatible coating of disposables and the application of various pharmacological agents. Biocompatible coated surfaces are designed to mimic physiologic surfaces. This study was designed to ascertain the effects of using coated circuits during pediatric CPB. After Institutional Review Board approval and parent/guardian consent, patients undergoing CPB, weighing less than 15 kg, with target CPB temperatures more than 28 degrees C, were enrolled into the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2-methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n = 16). Those patients were retrospectively matched to control patients having the same congenital repair with respect to patient size, surgeon, anesthesiologist, bypass time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n = 16). CPB data collected included on-bypass platelet count, hematocrit (HCT), and CPB blood product use. Postprotamine data collected in the operating room included blood product use, time from initial protamine administration to chest closure, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Postoperative intensive care unit (ICU) data included blood product use, HCT, chest tube output, platelet count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4, 6, 12, and 24 hours. Other data collected included intubation time, length of time to chest tube removal, and length of ICU stay. Statistical significance (p < .05) was seen in units of platelets transfused postprotamine, ventilator peak inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2, 4, 6, and 12 hours postoperative. Several parameters approached statistical significance, including PRBC transfused postprotamine, time from protamine administration to chest closure, postoperative day 0 platelets transfused, and ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used safely during pediatric heart surgery, resulting in a decrease in postoperative blood product use, improved postoperative lung function, and a reduction in the time spent in the ICU.