Background: This study aimed to determine the clinical efficacy of various immune interventions on mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Methods: We retrieved different immune strategies on how to prevent MTCT reported in the literature from Chinese and English electronic databases from the viewpoint of intrauterine and extrauterine prevention. Relative risk (RR) and 95% confidence interval (CI) methods were used. Results: Twenty-five articles on intrauterine prevention and 16 on extrauterine prevention were included in the analysis. Intrauterine prevention could reduce infants' HBV infection rate (RR = 0.36, 95% CI: 0.28-0.45) and increase their anti-hepatitis B surface-positive rate (RR = 2.42, 95% CI: 1.46-4.01) at birth. Compared with passive immunization, passive-active immunization could reduce infants' HBV infection rate (RR = 0.66, 95% CI: 0.52-0.84) at birth, even at more than 12 months of age (RR = 0.54, 95% CI: 0.42-0.69). Subgroup analysis demonstrated similar results except for pregnant women who were hepatitis B surface antigen-positive. Funnel plots and Egger's tests showed publication bias mainly in intrauterine prevention not in extrauterine one. Conclusions: The long-term protective effect of pregnant women injected with hepatitis B immunoglobulin during pregnancy should be further validated by large-scale randomized trials. Newborns of pregnant women who carried HBV should undergo a passive-active immunization strategy. Copyright © 2014 Jin et al.; licensee BioMed Central.