Hemolytic-uremic syndrome (HUS) is a well-recognized and rare complication occurring in renal transplant recipients treated with cyclosporine. Although direct endothelial injury probably plays an important role in this setting, cyclosporine may also increase platelet aggregation. This form of HUS is often, but not always, reversible with discontinuation of cyclosporine. The replacement of cyclosporine with non-nephrotoxic immunosuppressive agents may ameliorate renal dysfunction among patients with cyclosporine-induced nephrotoxicity. We report here about a 37-year-old male renal transplant recipient receiving cyclosporine who developed HUS in the early post-transplant period, which recovered on drug withdrawal and change cyclosporine to sirolimus. This case highlights the need to maintain a high index of suspicion in postoperative patient with anemia that resistance to erythropoietin therapy. Also in cases of acute graft deterioration with hemolysis and thrombocytopenia, cyclosporine should be stopped and other alternative immunosuppressants should be given.