Clinical and biological assessment of the COVID-19 vaccine efficacy in the frail population is of crucial importance. The study focuses on measuring the levels of anti-SARS-CoV-2 IgG antibodies before and after BNT162b2 mRNA COVID-19 vaccination among long-term care facility (LTCF) elderly residents. We conducted a prospective, single-center, observational study among LTCF residents. The study protocol was based on three blood sample acquisitions: first taken at baseline—5 days before the first dose of the vaccine, second—20 days after the first dose, and third—12 days after the second shot of the vaccine. The comparison was made for two cohorts: patients with and without prior COVID-19 infection. The data was collected from January to March 2021. A total number of 78 LTCF residents (55 women and 23 men) aged 62–104, 85.72 ± 7.59 years (mean ± SD), were enrolled in the study. All study participants were investigated for the presence of SARS-CoV-2 anti-spike (S) protein IgG, using a chemiluminescent immunoassay. Frailty was assessed with the Clinical Frailty Scale. Among elderly COVID-19 survivors in LTCF, a single dose of vaccine significantly increased anti-SARS-CoV-2 IgG antibody levels. IgG concentration after a single and double dose was comparable, which may suggest that elderly COVID-19 survivors do not require a second dose of vaccine. For residents without a previous history of COVID-19, two doses are needed to achieve an effective serological response. The level of anti-SARS-CoV-2 IgG antibodies after vaccination with BNT162b2 mRNA COVID-19 did not correlate with the frailty and age of the studied individuals.