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The pandemic of coronavirus disease 2019 (COVID-19) posed a severe threat to the public healthworldwide. We focus on frail elderly adults who are the most vulnerable population, especially residents of long-term care facilities or nursing homes. Studies have shown a strong correlation between frailty and COVID-19 mortality in the older population. Meanwhile, older adults possess various characteristics in immune responses, symptoms presentation, and disease outcomes. Frailty decreases resilience in older people and makes the situation more complex. Moreover, frailty is a strong predictor of prognosis in COVID-19 infected patients. Vaccination is considered an excellent way to stop SARS-CoV-2 spreading. Frail elderly adults are the most vulnerable population, and vaccination programs are implemented first in this group. However, most clinical trials did not enroll frail elderly adults in studies of COVID-19 vaccine development. Real-world evidence of vaccination in older adults with frailty is scanty.We reviewed available data from long-term care  facilities and nursing homes. We focused on immune responses, vaccine effectiveness, and safety of the COVID-19 vaccine. Vaccination could elicit antibody titers and cellular T cells responses in frail elderly adults. SARS-CoV-2 infection, hospital admission, and mortality in residents and staff in long-term care facilities were decreased. COVID-19 vaccination was safe and could prevent disease outbreak in long-term care facilities. Nevertheless, doctors should evaluate frailest or terminal elderly adults carefully. Frailty-based vaccination program could help to evaluate who should receive the COVID-19 vaccine.