Recombinant Human Erythropoietin (EPO) is extensively used for anemia in renal failure patients. It is normally safe and effective, improving symptoms of anemia. We report here a case of renal anemia in a patient undergoing peritoneal dialysis (PD) for end stage renal failure from renovascular disease. He initially responded well to Epoetin alpha (Eprex) but subsequently developed EPO antibodies and pure red cell aplasia (PRCA), becoming blood transfusion dependent. Subsequently, he responded to Darbepoetin alpha (Aranesp), without any complications in the presence of persisting EPO antibodies. This positive response, which restored hemoglobin values to normal, occurred despite general belief that any form of EPO will cross-react to EPO antibodies. This is the first case report where PRCA with EPO antibodies responded well to another EPO preparation without intervention from immunosuppression therapy.