Whole blood transfusion generates an inflammatory response and may contribute to organ dysfunction following cardiopulmonary bypass. We established a miniaturized (minimum 140 mL) and biocompatible bypass system to reduce perioperative inflammatory responses and avoid blood transfusions. This study was designed to reveal the influences of stored red blood cell (RBC) transfusions on perioperative inflammatory responses in infants. Fifty-four consecutive patients weighing 4-10 kg who underwent surgical procedures for complex heart anomalies with asanguineous prime were retrospectively reviewed. Twenty-two patients (40.7%) received RBC transfusions during CPB. The postoperative peak white blood cell count (p-WBC), peak neutrophil count (p-NC), and peak C-reactive protein (p-CRP) were compared for both patient groups. Stepwise multiple logistic regression analyses were used to investigate which of the factors most affected the perioperative inflammatory responses. The p-CRP and p-NC in patients with transfusion was significantly greater than those in patients without transfusion (CRP 8.1 +/- 5.1 versus 5.5 +/- 3.0 mg/dL, P < 0.05, p-NC 14.6 +/- 4.5 versus 12.0 +/- 4.0 x 1000/mm3, P < 0.05). Multivariate analyses showed that RBC transfusion most affected p-WBC (coefficient: 3.89, 95% confidence interval [CI] 0.79-6.99, P = 0.015) and p-NC (coefficient: 3.64, 95% CI 0.87-6.40, P = 0.011). The RBC transfusions increased the perioperative inflammatory responses, compared to transfusion-free procedures, even when using a miniaturized biocompatible bypass with an asanguineous prime.