BACKGROUND This randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT). MATERIAL AND METHODS Seventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the "EVL group" (n=38) and the "TAC group" (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group. RESULTS The 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively). The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group. CONCLUSIONS EVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.