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During the COVID-19 pandemic, no country with widespread community transmission has avoided outbreaks or deaths in residential aged care facilities (RACFs). As RACF residents are at high risk of morbidity and mortality from COVID-19, understanding disease severity risk factors is imperative. This retrospective cohort study aimed to compare COVID-19 disease severity (hospitalization and deaths) and associated risk factors among RACF residents in Victoria, Australia, across Delta and Omicron epidemic periods. Resident case hospitalization risk (HR) and case fatality risk (CFR) were assessed using Victorian RACFs COVID-19 outbreaks data across 2 epidemic periods; Delta, 994 resident cases linked to 86 outbreaks; and Omicron, 1882 resident cases linked to 209 outbreaks. Adjusting for outbreak-level clustering, age, sex, up-to-date vaccination status, and time since last vaccination, the odds of hospitalization and death were compared using mixed effects logistic regression. The HR and CFR was lower during the Omicron period compared with the Delta period [HR 8.2% vs 24.6%, odds ratio (OR) 0.17, 95% CI 0.11-0.26, and CFR: 11.4% vs 18.7%, OR 0.40, 95% CI 0.28-0.56]. During both periods, males had higher odds of hospitalization and odds of death; being up to date with vaccination reduced odds of hospitalization by 40% (excluding nonemergency patient transfers) and odds of death by 43%; and for each month since last vaccination, odds of hospitalization increased by 9% and odds of death by 16%. This study provides empirical evidence of lower COVID-19 severity among RACF residents in the Omicron period and highlights the importance of up-to-date and timely vaccination to reduce disease severity in this cohort. [ABSTRACT FROM AUTHOR]