There is currently limited data on the effectiveness of COVID-19 vaccines for children aged 6–11 years in Malaysia. This study aims to determine vaccine effectiveness (VE) against COVID-19-related hospitalization after receipt of one- and two-doses of BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine over a duration of almost 1 year in the predominantly Omicron period of BA.4/BA.5 and X.B.B sub lineages. This study linked administrative databases between May 2022 and March 2023 to evaluate real-world vaccine effectiveness (VE) for the BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine against COVID-19-related hospitalization in the Omicron pre-dominant period with BA.4/BA.5 and X.B.B sub lineages. During the Omicron-predominant period, the cumulative hospitalization rate was almost two times higher for unvaccinated children (9.6 per million population) compared to vaccinated children (6 per million population). The estimated VE against COVID-19 hospitalization for one dose of BNT162b2 was 27% (95% CI − 1%, 47%) and 38% (95% CI 27%, 48%) for two doses. The estimated VE against hospitalization remained stable when stratified by time. VE for the first 90 days was estimated to be 45% (95% CI 33, 55%), followed by 47% (95% CI 34, 56%) between 90 and 180 days, and 36% (95% CI 22, 45%) between 180 and 360 days. Recent infection within 6 months does not appear to modify the impact of vaccination on the risk of hospitalization, subject to the caveat of potential underestimation. In our pediatric population, BNT162b2 provided moderate-non-diminishing protection against COVID-19 hospitalization over almost 1 year of Omicron predominance.