Introduction. The lack of effective aetiotropic therapy of COVID-19 prompted researchers around the world searching for various methods of SARS-CoV-2 elimination, including convalescent plasma. The aim of this work was to study the safety and efficacy of severe COVID-19 treatment with convalescence plasma containing specific antibodies to the receptor binding domain (RBD) of SARS-CoV-2 S protein in a titer of at least 1: 1000. Methods. A single-center, randomized, prospective, clinical study performed at the FRCC FMBA of Russia with the participation of 85 patients who were stratified in two groups. The first group contains 20 critically ill patients who are on mechanical ventilation; Results. The use of plasma of convalescents in patients with severe COVID-19 with mechanical ventilation does not affect the disease outcome in these patients. Mortality rate in this group was 60%, which corresponds to the average mortality of patients on mechanical ventilation in our hospital. In the second group clinical improvement was detected in 75% and 51%, for convalescent and normal plasma respectively. Of the 46 people who received convalescent plasma, three patients (6.5%) were transferred to mechanical ventilation, two of whom died. In the group receiving non-immune plasma, the need for mechanical ventilation also arose in three patients (15%), of which two died. The hospital mortality in the group of convalescent plasma was 4.3%, which is significantly lower than the average COVID-19 hospital mortality in our Center (6.73%) and more than two times lower than the hospital mortality in the control group (n = 150), matched by age and by the disease severity. Conclusions. Thus, we demonstrated relative safety of convalescent plasma transfusion and the effectiveness of such therapy for COVID-19 at least in terms of the survival of patients with severe respiratory failure without mechanical ventilation. In the absence of bioengineered neutralizing antibodies and effective aetiotropic therapy, the use of hyperimmune convalescent plasma is the simplest and most effective method of specific etiopathogenetic therapy using forms of COVID-19.