The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.