Corticosteroids are an essential component of most immunosuppressive regimens currently used in renal transplantation because of their efficacy in reducing acute rejection and improving graft survival. Steroids, however, are associated with numerous side effects that lead to increased patient morbidity and mortality. The incidence and economic cost of steroid-related side effects have not been quantitatively assessed. Thus, based on a systematic review of the published literature, we estimated the incidence of steroid-related hypertension (15%), posttransplantation diabetes mellitus (10%), peripheral fractures (2% per year), avascular necrosis of the hip (8%), and cataracts (22%). In addition, we estimated that approximately 5% of patients who have cataracts or avascular necrosis of the hip require surgery. We used these literature-based estimates in a model to project the costs of treating side effects over a 10-year posttransplantation time frame for a 50-patient cohort that represented an average-sized renal transplant center. Steroid-induced hypertension and its complications were the most expensive side effect ($93,900), followed closely by posttransplantation diabetes ($89,700) and avascular necrosis of the hip ($61,700). Cataracts and peripheral bone fractures were less costly ($16,300 and $4,300, respectively). The cumulative projected 10-year cost of all side effects for the 50-patient cohort was $265, 900, or $5,300 per transplant patient. Steroid-related side effects add to the long-term cost of medical care of renal transplant recipients. These costs provide a rationale for further investigation of steroid-sparing immunosuppression protocols.