Objective To assess the safety and efficacy of convalescent plasma (CP) transfusion in elderly people with moderate to severe COVID-19 living in a long-term care facility (LTCF). Patients and Methods Twenty-two consecutive elderly COVID-19 patients living in a LTCF in Lombardy (Italy) who were given CP during the period May 15-July 31, 2020 were enrolled in a prospective cohort study. Their clinical, instrumental and laboratory parameters were assessed following the CP treatment. Overall mortality rate in this group was compared with that recorded in other LCTF in Lombardy during the 3-month period from March-May 2020. Results Of the 22 patients enrolled, 68.2% (n=15) received one CP unit, 27.3% (n=6) received two units and 4.5% (n=1) received three units. Of the CP units transfused, 76.7% (23/30) had a neutralizing antibody titer ≥1:160. No adverse reactions were recorded during or after CP administration. Improvements of clinical, functional, radiological and laboratory parameters during the 14 days following CP transfusion were observed in all 19 patients who survived. Viral clearance was achieved in all patients by the end of follow-up (median 66 days, IQR 48-80 days). The overall mortality rate was 13.6% (3/22), which compared favorably with that in the control group (38.3%, 281/733, P=0.02) and corresponded to a 65% reduction of mortality risk. Conclusion Early administration of CP with an adequate anti-SARS-CoV-2 antibody-titer to elderly, symptomatic, COVID-19 patients in a LTCF was safe and effective in eliminating the virus, restoring patients’ immunity and blocking the progression of COVID-19, thereby improving patients’ survival.