The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3%-28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4%-96.3%) and 95.8% (95% CrI: 95.5%-96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.Copyright © 2021. Published by Elsevier Inc.