Abstract: Objective To investigate therapuatic effect of high-dose intravenous immunoglobulin (IVIG) for early management of ABO hemolytic disease of the newborn (ABO-HDN). Methods A total of 121 cases with ABO-HDN were randomly divided into treatment group (n=61) and control group (n=60). In addition to the routine treatment of the control group, IVIG were given at a daily dose of 400 mg/kg to the cases in the treatment group for 2-3 times, and therapuatic effects were evaluated and compared between the two groups. Results The serum total billirubin concentration on the third day after treatment (153.42±45.21 μmol/L) and mean daily serum total billirubin concentration reduction (56.49±24.05 μmol/L) in treatment group were lower than those in the control group (P<0.01). The jaundice resolution time (23.51±11.19 h) and the phototherapy time (3.01±0.89 h) for billirubinemia treatment in treatment group were shorter than those in the control group (P<0.01). The patients in the the treatment group had higher hemoglobin level after treatment (15.59±2.01g/L) than those of the control group (P<0.01). Conclusion High-dose IVIG can effectively arrest the progression of hemolytic disease, quickly reduce serum total billirubin concentration and shorten phototherapy time for early treatment of ABO-HDN.