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A large prospective study of steroid withdrawal was performed within the framework of the Collaborative Transplant Study to analyze long-term graft and patient outcome in renal and heart transplant recipients. Steroids were withdrawn no earlier than 6 months posttransplantation. A comparison of 7-year outcomes in renal transplant recipients (94% receiving cyclosporine; 97% Caucasian) showed a benefit of steroid withdrawal versus steroid continuation in retrospectively matched controls, for graft survival (81.9%± 1.8% vs. 75.3%± 1.2%, p = 0.0001), patient survival (88.8%± 1.5% vs. 84.3 ± 1.0%; p = 0.0016) and death-censored graft survival (91.8%± 1.3% vs. 87.9%± 1.0%: p = 0.0091). Steroid withdrawal was associated with improved graft survival in heart recipients also (76.2%± 2.4% vs. 66.9%± 1.7%, p = 0.0008). A total of 58.6% of renal recipients and 44.3% of heart recipients never required steroids during follow up. Rates of acute rejection and renal dysfunction did not differ between steroid-free and steroid-continuation groups. Steroid withdrawal was associated with significantly improved cardiovascular risk factors compared with steroid continuation. Rates of the development of osteoporosis and cataracts did not differ in the entire patient cohort, but were strikingly lower in patients taken off steroids during the first posttransplant year.