The aim of this study was to compare the efficacy and safety profiles of the tacrolimus formulations Prograf (twice-daily) and prolonged release Advagraf (once-daily), combined with methylprednisolone and mycophenolate-mofetil, in de novo kidney transplant recipients. Both formulations showed comparable adverse events, acute rejection rates and renal function. Initially higher doses and, due to greater interpatient variability, more frequent dose adjustments were required in the Advagraf group to reach the intended trough levels. Yet this variability turned lower in the course of the study compared to the Prograf group, which allowed less frequent monitoring and dose adjustments under Advagraf as a possible indicator for greater adherence under once daily medication. Both formulations showed comparable good results, also in special conditions as the living donor transplantation, the European-Senior-Program or highly sensitized patients.