BACKGROUND: The high prevalence of hepatitis B weighs heavily on public health in China. In 2009, a catch-up vaccination program for children aged 8-15y was implemented to curb hepatitis B, while the effectiveness of this intervention has not been investigated. We aimed to evaluate the effectiveness of catch-up vaccination on the incidence of hepatitis B in Guangzhou, China. METHODS: We obtained individual data of all hepatitis B cases from 2005 to 2019 in Guangzhou from Guangzhou Center for Diseases Control and Prevention. Based on daily reported number of cases, we constructed generalized linear models to estimate the effectiveness of the intervention on the incidence of hepatitis B in each age group from 11 to 25 years. We further estimated the age-standardized effectiveness. Finally, we examined the effectiveness in different subgroups by sex and clinical types of hepatitis B. RESULTS: A total of 58,204 hepatitis B cases among individuals aged 11-25y were reported in Guangzhou from 2005 to 2019, with an average annual age-standardized incidence of 117.30 cases per 100,000 individuals. The catch-up vaccination contributed to an age-standardized 20.02% (95% confidence interval: 15.97%, 23.87%) decrease in the hepatitis B incidence among individuals aged 11-25y and prevented an annual age-standardized average of 17.40 (95% empirical confidence interval [eCI]: 9.24, 23.78) cases per 100,000 individuals from hepatitis B during the study period. The intervention could better protect males (excess incidence rate [EIR]: -21.82 [95% eCI: -30.51, -10.15] cases per 100,000 individuals), and prevent chronic cases (EIR: -24.27 [95% eCI: -30.62, -16.09] cases per 100,000 individuals). CONCLUSIONS: The massive catch-up vaccination against hepatitis B among children plays an important role in alleviating the burden of hepatitis B.