We evaluate the 5-year results of a single-centre prospective randomized trial that compared cyclosporine microemulsion (CyA-me) in triple therapy (plus steroids and azathioprine) and Tacrolimus (Tac) in double therapy (plus steroids) for primary immunosuppression. One hundred adult patients undergoing liver transplantation were randomized to receive Tac (n=51) or CyA-me (n=49). Ten patients in group A, and thirty-one patients in group B had their main immunosuppressive agent switched. The switch was much more frequent from CyA-me to Tac (n=31; 62.3%), mainly because of lack of efficacy (n=12; 38.7%). Six of 10 patients were shifted from Tac to CyA-me for side effects. The clinical course of the majority of patients converted from CyA-me to Tac improved clearly after conversion. Donor age and acute rejection (number, severity and rejection free days) had a significative association with lack of efficacy in group B. In these series, the conversion to Tac from CyA-me could be accomplished safely, with an excellent long-term outcome.