Abstract: Objective To evaluate the immunization efficacy of three doses of recombinant hepatitis B vaccine in the newborns whose mothers were HBsAg positive, and provide evidence for the development of immunization protocol. Methods A total of 637 newborns whose mothers were HBsAg positive during pregnant or childbearing were selected from 2005 to 2007 and were divided into 3 groups to receive 5 g, 10 g and 20 g recombinant hepatitis B vaccine at 0, 1 and 6 months respectively. Blood samples were taken from them within 1-6 months after vaccination to detect HBsAg by microparticle enzyme immunoassay (MEIA) and anti-HBs by chemiluminescence analysis. Results The HBsAg positive rate was 3.80% for 5 g group, 4.64% for 10 g group and 2.89% for 20 g group. The anti-HBs positive rate was 66.30%for 5 g group, 89.29% for 10 g group and 91.33% for 20 g group. There was no statistical differences on HBsAg positive rates among three groups (2=0.881,P=0.644), while the differences on anti-HBs positive rates in three groups were statistically significant (2=53.183,P﹤0.001) and the geometric mean concentrations(GMCs)of the anti-HBs in both 10 g group and 20 g group were higher than that in 5 g group. Conclusion The efficacy of vaccination protocol of 10 g3 recombinant yeast derived hepatitis B vaccine and 20 g3 recombinant CHO hepatitis B vaccine is optimal.