Tacrolimus is a very potent drug for preventing all types of acute rejection after renal transplantation. The decrease of vascular rejection may have important long-term implications. This is demonstrated in the 3-year data of the U.S. multicentre trial, where a significant decrease of graft loss was observed in the tacrolimus patients compared to cyclosporine patients. Safety profiles of both drugs are the same, but there are some major differences in side effects. Hyperglycemia is more common during tacrolimus, but generally the induction of hyperglycemia is a dose-dependent reversible process, which leads generally to diabetes mellitus during high systemic exposure, in certain races and prediabetics. Gum hyperplasia and hirsutism are not seen during tacrolimus therapy and there is a more favorable cardiovascular risk profile during tacrolimus as compared to cyclosporine based immunosuppression.