ABO incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group compatible living donor. Using different desensitization strategies, most centres apply B-cell depletion with rituximab and maintenance immunosuppression with tacrolimus and MPA. This high load of total immunosuppression leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low dose CNI and the mTOR inhibitor Everolimus for our ABOi program. Here, we report the first 25 patients with a complete three year follow up treated with this regimen. 3-year patient and graft survival was 96% and 83%. The rate of acute T-cell mediated rejections was low (12%). CMV infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections. This article is protected by copyright. All rights reserved.