In spite of adequate immunoprophylaxis, perinatal transmission of hepatitis B virus (HBV) has not been completely eliminated. This study evaluated the factors associated with the failure of HBV immunoprophylaxis. The study participants were 144 children who were born to HBsAg-seropositive mothers of known HBeAg status and they had received HB immune globulin and HB vaccine within 24 hours after birth followed by two further administrations of HB vaccine as recommended. Seventeen of the children (11.8%) suffered immunoprophylaxis failure, defined by HBsAg-seropositivity. The rate of HBV immunoprophylaxis failure was 12%, 0%, 21%, 0%, and 27% among the children born to HBsAg-seropositive, HBeAg-seronegative, HBeAg-seropositive, undetectable HBV DNA, and detectable HBV DNA mothers, respectively. The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg-seropositivity and HBV DNA seropositivity. To identify those children at high risk of HBV immunoprophylaxis failure, maternal HBeAg and HBV DNA need to be assessed prior to childbirth.