Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.