Objective This study aimed to assess risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV) after immunoprophylaxis. Methods Risk factors for MTCT were assessed using a multivariate logistic regression model. Patients We enrolled 256 mother-child pairs with positive maternal hepatitis B surface antigens (HBsAg) between January 2010 and June 2013. All children received passive-active immunization after birth. The children were tested for HBsAg at birth and 6-12 months and/or 1-3 years of age. Results Among 256 children, 10 (3.9%) developed HBV infection, all of whom were born to hepatitis B e antigen (HBeAg)-positive mothers with a high HBV DNA level (median, 7.36; range, 6.75-8.00 log10 IU/ mL). A total of 20 mothers received antiviral treatment during pregnancy. The maternal viral load decreased from an average of 7.16 to 3.08 log10 IU/mL (p<0.0001) at delivery. The multivariate logistic regression analysis showed that a high maternal HBV DNA level [odds ratio (OR) for each log10 IU/mL increase, 2.44; 95% confidence interval (CI), 1.13-5.29, p=0.023] and vaginal delivery (OR=6.96, 95% CI, 1.80-26.93, p= 0.005) were risk factors for HBV immunoprophylaxis failure. Conclusion Additional treatment strategies should be considered in HBeAg-positive mothers with an HBV DNA level above 6-7 log10 IU/mL. In addition, our study supports the use of Cesarean section for infants born to HBsAg-positive mothers.