Cardio-pulmonary bypass is associated with a systemic inflammatory response syndrome characterized by complement activation, neutrophils activation, and the release of proinflammatory cytokines as TNF-α and IL-8. Pediatric patients are at higher risk of developing this response. The study was done on 40 pediatric patient and the patients were randomly divided into 4 equal groups: Group C: Control group, Group A: Aprotinin group, Received only Aprotinin, Group H : Hemofiltration group, Subjected only to hemofiltration, and Group AH: Aprotinin-Hemofiltration group. The levels of cytokines TNF-α and IL-8 were measured before bypass, after bypass, and after 24 hours, and correlated with the clinical outcome of patients. Results: In all groups of the study, levels of both TNF-α and IL-8 raised significantly one hour following exposure to CPB, and twenty-four hours after CPB the levels declined significantly but remained significantly higher than pre bypass values. The highest levels of TNF-α and IL-8 both post bypass and after 24 hours was found in the control group which showed the highest incidence of post-operative complications, and the longest ICU stay. Aprotinin was more efficient in blocking IL-8 release than TNF-α. Hemofiltration is more efficient in removing TNF- α than IL-8 from the circulation. In aprotinin- hemofiltration group, there was a highly significant reduction of both TNF-α and IL-8 compared to control group, and compared aprotinin and hemofiltration groups, both post bypass, and post 24 hours . The combined technique is more efficient in attenuation of inflammatory response than either both measures alone which was reflected by the highest post bypass systolic and diastolic blood pressure among the four groups with the least dose dopamine and SNP, higher oxygen saturation, shorter duration of postoperative mechanical ventilation and of ICU stay, and least incidence of complications among the 4 groups. Conclusion: The concomitant use of both aprotinin and hemofiltration is an efficient measure to ameliorate the systemic inflammatory response syndrome in pediatric patients undergoing surgical correction of acyanotic congenital heart diseases and subjected to CPB, and this technique is superior than using either aprotinin or hemofiltration alone in attenuation of the systemic inflammatory response syndrome.