INTRODUCTION: Evidence of the waning immunity of coronavirus disease 2019 (COVID-19) primary vaccination, and immune evasion by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to the rollout of booster vaccination in many countries. Assessing the effectiveness of booster vaccination against severe COVID-19 outcomes is crucial during the transition to endemicity. METHODOLOGY: We conducted a population-based, matched case-control study in Malaysia to estimate the marginal vaccine effectiveness (mVE) of homologous and heterologous BNT162b2 and CoronaVac booster vaccination against COVID-19 related intensive care unit (ICU) admission and death in Delta-predominant and Omicron-predominant periods. RESULTS: Receipt of a booster vaccination - either homologous or heterologous for CoronaVac, and homologous for BNT162b2 - demonstrated mVE estimates of at least 70% against ICU admission and at least 80% against death, compared to BNT162b2 primary vaccination, in both periods. Overall, the mVE estimates were 10-20 percentage points lower in the Omicron-predominant period than in the Delta-predominant period. CONCLUSIONS: Our study reaffirms that the administration of booster vaccination increases protection against severe COVID-19 outcomes for BNT162b2 and CoronaVac primary vaccination recipients.