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A repeat renal transplantation is believed to confer the best survival advantage for allograft failure. The scarcity of matching donors at one end, coupled with the expanding pool of ABO-incompatible (ABOi) donors at the other end, lead us to consider the option of ABOi kidney re-transplantation. However, ABOi kidney re-transplantation is associated with heightened immunological risk due to the presence of two substantial immunological barriers. Concern, queries, and uncertainty exist over the course and outcome of this option. We prospectively studied five patients who underwent live-related ABOi re-transplantation after a failed previous transplant. Four patients (mean age 40.8 ± 6.6 years, 4 males) underwent a second renal transplant, whereas one patient had a third renal transplant. All patients received desensitization with rituximab, plasmapheresis, and intravenous immunoglobulin as per routine protocol. One patient required immunoadsorption to achieve the desired Anti-ABO titer. All five patients had good graft survival. One of them developed combined antibody and cell-mediated rejection and another antibody-mediated rejection. Live-related ABOi kidney re-transplantation could be a viable option for patients with a previously failed graft., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Nephrology.)