Background and study aim: Hepatitis B vaccination has been included in routine infant's immunization in Egypt since 1991. Although it could provide high levels of sero-protection, the duration of that protection remains largely unknown. The aim of this study was to evaluate the initial immunoprophylaxis response to compulsory hepatitis B vaccination and its long term protection in Egyptian children. Patients and methods: Antibodies to hepatitis B surface antigen (anti-HBs) was assessed in 200 apparently healthy Egyptian children.They were all vaccinated with hepatitis B vaccine in infancy through the compulsory vaccination program. They were classified into two groups, each contained 100 children. The 1st group included infants at least 2 months after completion of the 3 doses of the vaccine (≥8 months old). While the 2nd group included children aged 6-12 years old. Sera were obtained from all children and were tested for anti-HBs titer, HBsAg and antibodies to hepatitis B core antigen (anti-HBc) by ELISA. Children who were discovered to have non-protective titers (≤10 mIU/mL) received a booster dose of the vaccine and were re-evaluated within 2-4 weeks. Different factors associated with poor immune response were analyzed. Results: The initial responders rate of 83% was detected in group І which was significantly higher than that in group П of only 52%. Moreover, mean titer of Anti-Hbs was significantly decreased with age,( 48.9 ±15.8 mIU/ml in group І vs 12.6 ± 5.2 mIU/ml in group II). Also, within the 2nd group, a negative correlation between Anti-HBs mean level and age in years was displayed. No significant difference could be detected in the percentage of infected children between both groups (4% in group I vs.6% in group IІ). Sixty two percent of the boosted children showed a significant increase in their mean anti-HBs titer. Male gender and rural residence were associated with poor vaccine response in both groups. Conclusion: As maternal screening is not feasible in our country, Hep-B vaccine birth dose is a necessity to prevent perinatal infection. Most of infants vaccinated with compulsory Hep-B vaccine retained their immune protection years after vaccination either by high antiHBs titer or efficient memory T cells. However, large scale and long term follow up study is still needed before clearly answering the question about the need for booster dosing and its proper timing.