In order for liver cirrhosis and hepatocellular carcinoma not to be inflicted upon in infants’ lifetime, it is essential to prevent hepatitis B virus (HBV) infection in them.The aim of this study is to reveal the efficacy of passive and active immunoprophylaxis in preventing perinatal transmission of HBV in Iran.In this cohort study with historical controls, 823 children born to the HBsAg positive mothers were evaluated. Out of this number, 638 had received neither hepatitis B (HB) vaccine nor hepatitis B immune globulin (HBIG) and aged more than 16 years (n=481, group 1) or 16 years or less (n=157, group 2). The other 125 persons had received only HB vaccine (group 3), and 60 neonates received both HB vaccine and HBIG (group 4).The prevalence of HBsAg in groups 1, 2, 3 and 4 was 56.1%, 40.3%, 12.6%, and 3.6%, respectively. The prevalence of anti-HBsAb had a significantly descending rate in groups 4 (85.7%), 3 (68.8%), 2 (33.3%), and 1 (21.8%), respectively.The addition of HBIG to recombinant vaccine will significantly increase the protection against HBV infection in comparison with HB vaccine alone.