Abstract: Background: Hepatitis B is a vaccine-preventable liver infection caused by the Hepatitis B Virus (HBV). Hepatitis B (HB) is spread when blood, semen, or other body fluids from a person infected with the virus enters the body of someone who is not infected. Aim of the study: To identify the efficacy of hepatitis B immunoglobulin with hepatitis B vaccine versus hepatitis B vaccine alone to prevent the HB vertical infection. Method: An quasi-experimental clinical trial was used, 114 new born were included in the control group and 114 newborn were included in the intervention group, both groups were given HB vaccine but the control group HB vaccine combined with hepatitis B immunoglobulin, all of the subjects were born to mother positive HBV and negative HBeAg indicating inactive HBV cases. Results: Revealed that the used regimens were effective to interrupt mother to child transmission of HBV, the geometric mean titration was higher (207.64 IU/L) among the infants were included in the control group versus (180.87 IU/L) to the infants were included in the intervention group, non-protective rate was 6.6%, relative risk 2.63. Conclusion: Hepatitis B vaccine alone is not inferior to HB vaccine combined with HBIG to prevent the infection and both regimens were effective.