Abstract Hepatitis B virus (HBV) infection is highly prevalent in Asia, Africa, southern Europe and Latin America, HBV vaccination has effectively reduced the acute and chronic infection rates as well as related complications in the vaccinated children. The incidence of hepatocellular carcinoma in children has been reduced to approximately 25% of the incidence before the vaccination program, and fulminant hepatitis in children has also been reduced after universal hepatitis B vaccination. HBV DNA sero-positive rate was 98–100% in HBsAg positive vaccinated children, while the positive rate was only 11–20% in those vaccinees with a negative HBsAg but positive anti-HBc reaction. Hepatitis B surface gene mutants in HBV DNA positive children increased gradually from 7.8% before the vaccination program, to 19.6%, 28.1% and 23.1% at 5, 10 and 15 years after the vaccination program. Long-term follow-up of vaccinated children has confirmed that universal HBV vaccination in infancy has produced adequate protection up to 14 years of age. The annual decay rate of hepatitis B surface antibody (anti-HBs) was 10.2% in children who did not receive a booster dose. The new HBV infection rate was not different between those who did and those who did not receive a booster dose of HBV vaccine. During a follow-up period of seven years for 1200 vaccinated 7-year-old children in Taiwan, the mean annual hepatitis B core antibody sero-conversion rate was 0.2%. All were negative for HBV DNA. No new chronic HBV infections developed. A booster dose of HBV vaccine is not recommended in children under 15 years of age. Systematic HBV DNA screening of a large population such as blood donors may be instrumental in following the long-term effect of the universal vaccination program on the incidence of silent HBV infection and vaccine escape mutants.