Kidneys from marginal donors may be particularly susceptible to calcineurin inhibitor (CI)-mediated nephrotoxicity. To avoid CI nephrotoxicity, CI-free protocols have been introduced as maintenance immunosuppressive therapy. A CI-free protocol of ATG induction, sirolimus (SRL), mycophenolate mofetil (MMF) and steroids, has been adopted at our center in recipients of a DKT from elderly donors. DKT from October 1999 to December 2002 (GroupI=23) receiving CI-therapy were reviewed and compared with DKT performed subsequently until June 2004 at our institution, receiving a CI-free immunosuppression (GroupII=13). Patient and graft survival, surgical and medical complications, rejection episodes and renal function were retrospectively analyzed. After a mean follow-up of 42 ±11 months (GroupI) and 8 ±4 months (GroupII) no deaths occurred. Graft losses occurred in 3 patients of GroupI (1 PNF, 1 chronic rejection, 1 Kaposi’s sarcoma) and in 1 patient of GroupII (venous thrombosis). Acute rejection incidence was 17.4% in GroupI and 30.8% in GroupII. ATN was 60.9% and 7.7%, respectively. Renal function was better in GroupII with a mean S-Cr at 1 and 6 months of 215 ±143 µmol/L versus 137 ±52 µmol/L and 151 ±49 µmol/L vs 108 ±28 µmol/L respectively. In GroupII, 4 patients were switched to tacrolimus because of acute rejection and 2 patients to cyclosporine (1 pancytopenia, 1 arthralgia). DKT from elderly donors provides excellent results in terms of graft function. An immunosuppressive regimen including anti-lymphocyte antibodies-induction, SRL, MMF and steroids, permits to reduce the incidence of ATN providing an optimal graft function.