Introduction: Perinatal vertical transmission is the most common mode of transmission worldwide. Antenatal screening is recommended. Immediate treatment of the infant born to an HBsAg-positive mother, using HBIG (hepatitis B immunoglobulin) and HBV (hepatitis B virus) vaccine can abort acquisition.The aim of this work (specific objectives): is to identify possible maternal risk factors for HBV acquisition, introduce a model for prevention of vertical transmission of HBV and to assess the efficacy of active and passive immunoprophylaxis administered within the first 12-48 hours after birth to infants born to HBsAg positive mothers.Patients and methods: Two thousand pregnant women performing routine antenatal care at the outpatient clinic of the Obstetrics department of Cairo University and Center for Social and Preventive Medicine were screened for HBsAg. Screening was carried out from May 2010 to July 2011. The study as well included pregnant women known to have HBV infection. Positive tests were repeated using enzyme immunoassay for confirmation. A questionnaire about the possible risk factors for acquisition of HBV infection was filled for every pregnant HBsAg positive female in addition to at least 2 pregnant HBsAg negative females for each positive case.Newborns encountered within the first 48 hours after delivery received both 0.5 ml of HBIG and 0.5 ml of recombinant HBV vaccine intramuscularly at two different sites. They received two booster doses of HBV vaccine at the age of 1 and 6 months. All newborns given immunoprophylaxis were tested for HBV viral load by quantitative real time PCR at birth. At six months of age, the infants were tested for HBsAg and HBsAb.Results: Confirmatory tests were positive in only 23 screened mothers. The history of injections, medical clinic attendance and previous hospital admission, was statistically significant (p<0.001) between both HBsAg positive (n=35) and negative pregnant females (n=82). The history of previous surgeries was also significant (p=0.003). Both HBIG and HBV vaccine were administered to 31 (91.17%) newborns within the 1st 48 hours after birth, while 3 (8.83%) received the vaccine only. Among the 31 infants: 25 became seropositive for HBsAb and were negative for HBsAg, 1 was seronegative to HBsAb after 4 doses of the vaccine, 1 became HBsAg positive and 4 were lost to follow up at 6 months. The success rate of our immunoprophylaxis was 92.6 %.Conclusion: Early immunoprophylaxis is effective in the prevention of vertical transmission of HBV with a success rate of 92.6%.