COVID-19 severely affected nursing home residents from March 2020 onwards in Belgium. This study aimed to model the impact of vaccination and facility characteristics on cluster occurrence, duration and severity in this setting. Possible clusters were identified between June 2020 and January 2022, based on the Belgian COVID-19 surveillance in nursing homes. Median attack rates (AR) among residents and staff, case hospitalization rates (CHR) and case fatality rates (CFR) were calculated. A negative binomial model was used to identify the association between nursing home characteristics and the number of cases, hospital admissions and deaths and the duration of the cluster. A total of 2,239 clusters were detected in more than 80% of nursing homes. Most of these (62%) occurred before the start of COVID-19 vaccination (end of December 2020). After vaccination, the number of clusters, the AR among residents and staff, the CHR and the CFR dropped. Previous cluster(s) and vaccination decreased the number of cases, hospital admissions and deaths among residents. Previous cluster experience and having started vaccination were protective factors. We recommend continued implementation of targeted interventions such as vaccination, large-scale screening and immediate implementation of additional infection prevention and control measures.