Patients with beta-thalassemia major are at risk of Hepatitis B viral infection due to repeated transfusion. We followed 158 patients vaccinated at our center at 0, 1 and 6 months. Those younger than 10 years received 10 micrograms. Those 10 years and older, received 20 micrograms. A group of children younger than 10 years were randomly allocated to receive 20 micrograms. The response to the vaccine was excellent at 6 months after the third dose, in the whole study population. The higher dose was more immunogenic in children <10 years, yet the 10 micrograms dose was equally protective after 5 years follow-up. Those 10 years and older showed rapid loss of antibodies, where 45% became non-immune by the 3rd year. All those who lost immunity had titer 10-99 mIU/ml, except one. No evidence of hepatitis B virus infection was observed over the follow-up period among the respondent vaccinees. We conclude that the vaccine is immunogenic and protective in thalassemic children. Ten micrograms seems adequate for long-term protection in those younger than 10 years. A fourth dose of 20 micrograms for those 10 years and older needs to be tried to ensure long-term protection for this age group.