Objective To investigate the feasibility and effectiveness of synchronizing replacement of peripheral blood in treating neonates with hyperbilirubinemia.Methods A catheter was inserted into a scalp temporal vein for infusion of donor blood,meanwhile another catheter connecting three way stopcock was inserted into a femoral artery withdrawing about 1.5~2.0 times of internal blood volume.Vital signs were monitored electronically and recorded.Blood routine,reticulocytes,liver function,blood biochemistry and so on were measured before and after transfusion.Results The mean drop in serum bilirubin concentration was(47.29±13.43)% after exchange transfusion,mainly in hemobilirubin.Hb,RC,Na+,Ca2+ descended significantly(P<0.01),and WBC also descended significantly(P<0.05),and Glu heightened obviously(P<0.01) after replacement transfusion.Average blood volume exchanged was 135 ml·kg-1.20 cases improve the general state of health and internal environment rapidly after treatment,only 2 persons had hyperglycosemia shortly,and became usual after an hour by intravenous dropping insulin.Conclusion The synchronizing replacement transfusion of peripheral blood is practicable and safe with few complications,which is recommended to be widely used.