BACKGROUND In the present era, kidney transplantation across immunological barriers (ABO incompatibility and human leucocyte antigen (HLA) incompatibility) is a successful strategy to provide transplantation to immunologically high-risk patients. The safety and outcome of crossing both ABO and HLA barriers simultaneously in a retransplantation scenario is rarely reported from the developing world. CASE REPORT A 30-year-old female underwent a third living donor kidney transplantation. Her previous 2 transplants being lost to chronic allograft nephropathy. The transplantation was done across a simultaneous blood group as well as HLA incompatibility. The donor was the mother who was blood group B, with the recipient being blood group O. The complement dependent cytotoxicity crossmatch of the pair was negative but the flow cross match for T as well as B lymphocytes was positive. The mean fluorescence intensity value for class I antigens was 6951 and that for class 2 antigens was 7534. The patient underwent a desensitization procedure including rituximab, plasmapheresis and intravenous immunoglobulin pre-transplantation. The pre-transplantation isohemaglutunin titer was <1: 8 and the donor specific antibody against class 1 antigens was <2200 and <770 against class 2 antigens. Induction was done with anti-thymocyte globulin in the dose of 3 mg/kg in 2 divided doses. The patient is maintained on triple immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. After a follow-up period of 5 months, she maintains a good graft function with serum creatinine of 1.01 mg/dL. CONCLUSIONS With the advances in the desensitizing procedures in the developing world, kidney transplantation across a combined HLA and ABO incompatible barrier can be offered to these highly sensitized patients, even in case of retransplantation.