The aim of our study was to compare the efficacy of two dosages of hepatitis B immunoglobulin (HBIG) combined with HBV vaccine (HBVac) to prevent mother-to-child transmission (MTCT) of hepatitis B in HBsAg- and HBeAg-positive mother. We enrolled 331 mother-infant pairs with HBsAg- and HBeAg-positive maternal state from the Women's Hospital School of Medicine of Zhejiang University. Newborns were randomly distributed into two groups according to the dosages of HBIG injection: 100 IU and 200 IU. Newborns from both groups were injected with HBVac in the same doses. We compared the immune outcomes between the two groups and explore the influencing factors of immune outcomes through regression analysis. There was no statistically significant relationship between HBsAg serological transmission of newborns and dosages of HBIG in HBsAg- and HBeAg-positive mother (p > .05). The Logistic regression showed that high DNA load is a risk factor for passive-active immunoprophylaxis failure for both 100 IU and 200 IU group, but higher-dosage HBIG is not necessary for higher-viral-load pregnant women with HBsAg- and HBeAg-positive. In conclusion, combined application of HBVac and a single dose of 100 IU HBIG can achieve the ideal MTCT interruption results for HBsAg- and HBeAg-positive pregnant women.IMPACT STATEMENTWhat is already known on this subject? Passive-active immunoprophylaxis is proved to be effective in preventing mother-to-child transmission of hepatitis B. Hepatitis B vaccine combined with 100 IU or 200 IU immunoglobulin is mostly recommended in China.What do the results of this study add? At present, there is still a lack scientific basis for improving existing strategies and measures to prevent mother-to-child transmission of hepatitis B in China.What are the implications of these findings for clinical practice and/or further research? 100 IU and 200 IU immunoglobulin show equivalent blocking effect, and combined use of hepatitis B vaccine and 100 IU immunoglobulin is more cost-effective.