To investigate the role of graded reoxygenation with cardiopulmonary bypass (CPB) in prevention of reoxygenation injury in children with cyanotic congenital heart defects, and to evaluate its safety.Twenty pediatric patients with cyanotic congenital heart defect were randomly divided into 2 equal groups according to CPB methodology: group 1, undergoing routine hyperoxic CPB with CPB primed and initiated at FiO(2) of 1.0, and group 2 undergoing modified CPB with graded reoxygenation (CPB was primed and initiated at FiO(2) of 0.21 and the FiO(2) was increased slowly to 30% to 60% over the next 5 to 10 minutes). Serum troponin 1 (TnI), S100beta protein, and malondialdehyde (MDA) were measured before CPB, and 1 minute, 5 minutes, and 10 minutes after CPB. Near infrared spectroscopy (NIRS) was applied to evaluate the cerebral oxygenated hemoglobin (HbO(2)) and oxidized cytochrome aa3 (CytOx) and jugular venous lactate was measured during the reoxygenation period. Clinical indexes were observed.Before CPB the TnI, S100beta, and MDA levels in these 2 groups were all normal without significant differences between them. After initiation of CPB the TnI, S100beta, and MDA levels in the two groups began to increase. The serum Tn1 levels 1 minute and 5 minutes after the initiation of CPB of the group 1 were significant lower than those of the group 2 (both P < 0.01). The serum S100beta levels 1, 5, and 10 minutes after the initiation of CPB in the group 2 were all lower than those of the group 1 and there were significant differences between these 2 group 5 and 10 minutes after (both P < 0.05). The serum MDA levels 1, 5, and 10 minutes of the group 1 were significantly higher than those of the group 2 (all P < 0.05). NIRS showed that HbO(2) decreased slightly because of hemodilution when CPB was begun, and then increased rapidly 2 minutes after the initiation of CPB; and CytOx decreased progressively during the reoxygenation period, however, without significant difference between these 2 groups. The serum lactate level was markedly increased 1 minute after the initiation of CPB and then gradually decreased through the reoxygenation period, however, without significant differences between these 2 groups. There was no significant difference between the two groups in clinical observation.Not damaging the cerebral aerobic metabolism, graded reoxygenation with CPB can reduce the extent of reoxygenation injury of routine hyperoxic CPB and is an easy, effective, and safe CPB strategy.