Objective: To investigate the efficacy of 200IU hepatitis B immunoglobulin (HBIG) injection at 1 month after birth to interrupt the mother-to-children transmission (MTCT) of hepatitis B virus (HBV). Methods: Infants born to mothers who were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA load ≥1.0×10⁶ IU/ml and who did not receive antiviral drug treatment during pregnancy, were randomly divided into 2 groups. Infants in the control group were treated with standard immunoprophylaxis: 200 IU HBIG and 10 μg recombinant hepatitis B vaccine injection within 2 h after birth and a vaccine booster at 1 and 6 months after birth. For infants in the HBIG group the standard immunoprophylaxis and an additional 200 IU HBIG were administered at 1 month. HBsAg, the antibody to HBsAg (anti-HBs), and HBV DNA load were measured at birth and after 7 months. later.Immunoprophylaxis failure was defined as the presence of HBV DNA and HBsAg positivity or the presence of HBV DNA and HBsAg negativity at 7 months. Results: In this prospective cohort study, of the 280 infants enrolled, 14 infants (HBIG/control: 6/8) were lost to follow-up and 266 subjects (HBIG/control: 134/132) completed the 7-month study. The log₁₀HBV DNA load of mothers in the HBIG group and control group were (7.31±0.66) log₁₀IU/ml and (7.32±0.74) log₁₀IU/ml, respectively (P=0.92). The MTCT rate of the two groups was similar (5.97% vs. 7.58%, P=0.63). At 7 months, the HBsAg positive rate and the level of anti-HBs in the two groups were 94.03%(126/134)vs. 91.67% (121/132) and 623.60±412.93 mIU/mL vs. 620.38±399.10 mIU/ml, respectively with no significant difference (P=0.48 and P=0.95, respectively). The log₁₀ HBV DNA load of mothers in immunoprophylaxis failure group and success group was similar (P=0.09). The number of infants who were serum HBsAg positive and HBV DNA positive at birth in the immunoprophylaxis failure group were higher than those in the success group (100% and 100% vs. 35.89% and 31.85%, P<0.01, respectively). The serum HBsAg levels in infants at birth was the only independent relevant factor for HBV MTCT, with risk rates of 11.18 (95% Confidence interval (CI), 1.23-101.88), 352.00 (95%CI, 15.82-7833.20), and 968.00 (95%CI 81.35-11519.19) for HBsAg levels of 0.05-< 1, 1-< 10, and ≥ 10 IU/ml, respectively, compared to infants with HBsAg levels < 0.05 IU/ml. Conclusions Administering 200IU HBIG injection at 1 month did not reduce the risk of HBV MTCT.