BACKGROUND Calcineurin inhibitor drugs (CNI), which are the basis of immunosuppression in kidney transplantation, contribute to renal graft loss, with increased morbidity and mortality due to their potentially harmful effects on the renal graft, cardiovascular system, and tumor pathology. For this reason, the mammalian target of rapamycin inhibitors (mTORi) such as sirolimus (SRL) and everolimus (EVE) has been preferred more frequently, as they are associated with fewer complications and longer graft function. MATERIAL AND METHODS We enrolled 89 adult renal transplant patients (37 patients on mTORi and 52 on CNI) who had similar age, sex, primary renal disease, dialysis type, post-transplant follow-up period, and donor type. We analyzed and compared the data between patients using mTORi for longer than 5 years and those using CNI regarding pre- and post-transplant panel reactive antibody (PRA), and donor-specific antibody (DSA), as well as post-transplantation and current graft functions. RESULTS Although those using mTORi for more than 5 years had significantly higher mismatch rates (P=0.024) than those using CNI, there was no significant change in PRA and DSA levels. Transplant time was longer in mTORi users (P=0.025). The switch time to mTORi in patients ranged from 0 to 19 years, but the average was 4 years. As expected, actual spot urine protein/creatinine was significantly higher in those using mTORi (P=0.009). Diabetes mellitus (DM) and BK virus nephropathy (BKVN) rates were significantly higher due to switching the regimen from CNI to mTORi. CONCLUSIONS Long-term use of mTORi does not appear to be an immunological problem.