Purpose: to evaluate the efficacy of prolonged courses of systemically administered subtherapeutic Metipred and cyclosporine in prevention of graft rejection in high-risk children. Material and methods. The study included 27 children at high risk of graft rejection due to re-keratoplasty (n=8), limbo-keratoplasty for corneal staphyloma (n=4), or transplantation into vascularized corneal bed (n=15). All patients were divided into two groups - the study group (n=11) and the control group (n=16). In order to evaluate the efficacy of two different prevention schemes, the occurrence of graft rejection, rejection crises, and crisis-associated clouding of the transplant was analyzed. Results. The occurrence of transplant opacity was two times lower in the Metipred-cyclosporine group than in the conventional prevention group. Kaplan-Meier one-year survival of the transplant was 53% in the study group and 27% in the control group. Two-year survival rate difference appeared even more significant - 53% and 18% correspondingly. Conclusion. It is clinically shown that subtherapeutic use of Metipred and cyclosporine decreases the occurrence of rejection crises and transplant failure almost by half in high-risk patients as compared with topical corticosteroids; at the same time the side effects of systemic immunosuppression are not substantial. Thus, the suggested prevention scheme allows to perform keratoplasty and expect a clear transplant in children who previously were considered inoperable, i.e. with total vascularized corneal opacity, giant staphylomas, and corneal burns.