To evaluate the efficacy and safety of oral tacrolimus-based immunosuppressive induction therapy, 130 primary orthotopic liver transplant (OLT) recipients were randomised to treatment in an open, parallel-group, European multicentre trial. Following OLT, patients were immediately administered either tacrolimus (0.10 mg/kg) and prednisolone (dual therapy group) or tacrolimus (0.06 mg/kg) in conjunction with prednisolone and azathioprine (triple therapy group) both orally. Patient survival at 1 year was 79.4% for the dual therapy group and 88.7% for the triple therapy group (P = 0.194); 1-year graft survival rates were 76.5% in the dual therapy group and 80.6% in the group receiving triple therapy (P = 0.615). The frequencies of rejection (dual therapy 42.6%, triple therapy 50.0%; P = 0.482), infection, and other complications (renal, neurological and glucose metabolic disorders) were similar in both groups. Tacrolimus whole blood trough concentrations were detectable on days 1 and 2, respectively, in the dual and triple therapy treatment groups whilst median tacrolimus blood concentrations in the triple therapy group reached levels similar to those in the dual therapy group on postoperative day 11 following a steady increase in dose. After 1 year, 54.4% of the patients randomised to dual therapy were receiving tacrolimus monotherapy and only 56.4% of the patients randomised to triple therapy continued to receive azathioprine. In conclusion, oral tacrolimus-based immunosuppression is both potent and safe when administered as induction therapy after OLT. Treatment may commence at either 0.06 or 0.10 mg/ kg per day, but doses may need to be increased to the latter value within the first 10 days to maintain effective immunosuppression.