Background Diphtheria can be effectively prevented by adequate immunization. A combined vaccine against diphtheria toxoid, pertussis, and tetanus toxoid (DPT) is currently used in routine pediatric immunizations. Outbreaks of diphtheria could emerge in Indonesia as a consequence of declining routine vaccination during the COVID-19 pandemic. Objective To analyze the impact of the first (administered at 18-24 months of age) and second diphtheria boosters (administered at 5-7 years of age) in retaining protective levels of anti-diphtheria toxoid antibodies. We also investigated for relevant factors associ-ated with anti-diphtheria toxoid antibody titers. Methods This cross-sectional study was conducted in the Senen District of Jakarta, Indonesia. The inclusion criteria were healthy children aged 6 to 7 years with documented history of DPT vaccination. Primary vaccination defined as 3 doses of DPT at age less than 1 year, first booster was DPT vaccination at 18-24 years of age, and second booster was diphtheria-tetanus (DT) vaccination received at 5 to 7 years of age. Peripheral blood specimens were obtained from participating children, after informed consent was provided by their parents. Antibodies against diphtheria in sera specimens were assessed by commercial anti-diphtheria toxoid immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results There were 154 children included in the study, with a female majority (61%). Overall, specific humoral immunity against diphtheria was observed in 113 children (73.4%). There was no statistical difference in immunity level between genders. Importantly, children who received the first and second diphtheria booster had significantly higher anti-diphtheria antibody level than those who did not receive both diphtheria booster (P<0.001). Conc l us i on Boos t er vacci nat i ons ar e cr uci al among school-age chi l dren i n Indonesi a to i mprove thei r an-ti-diphtheria immunity and to minimize a risk of diph-theri a outbreaks. [Paedi atr Indones. 2024;64:447-53; DOI: https://doi.org/10.14238/pi64.5.2024.447-53 ]. © 2024, Indonesian Pediatric Society Publishing House. All rights reserved.