BACKGROUND AND PURPOSE: Nephrotoxicity caused by calcineurin inhibitors ( CNIs) contributes to chronic renal allograft dysfunction (CRAD). This retrospective cohort study evaluated the immunosuppressive and nephrotoxic effects of sirolimus add-on therapy with minimization of CNI in patients with CRAD. METHODS: Twenty patients with CRAD were recruited to receive sirolimus add-on rescue (SRL-AR) therapy. The SRL-AR therapy added 6 mg of sirolimus for loading and 2 mg/day for maintenance to CNI-based maintenance immunosuppressive regimens and reduced the dose of CNI, either cyclosporine or tacrolimus, by half at the initiation of sirolimus loading. The primary endpoint of the study was estimated glomerular filtration rate (GFR) determined using the Cockcroft-Gault formula. The efficacy of this SRL-AR therapy was evaluated by comparison to a historic group of 30 patients with CRAD who received a tacrolimus-based rescue therapy. RESULTS: Of the 20 patients receiving sirolimus therapy, 2 had graft failure during the 12-month follow-up. The post-rescue GFR values of the patients receiving sirolimus therapy showed greater improvement than those of the historic group during follow- up except for month 8, with the differences in GFR changes reaching significance at months 1 to 5 (p