We describe the case of a 24-year-old female with end-stage renal disease from focal segmental glomerulosclerosis (FSGS) diagnosed at age 16, who underwent monozygotic triplet transplantation at age 21 from her sister. Monozygosity was established by buccal smear DNA PCR amplification using short tandem repeat (1) profiling for 16 genetic alleles. All immunosuppression was discontinued by 1 month posttransplant. To evaluate the use of immunosuppression in HLA identical monozygotic transplantation, we interrogated the OPTN (Organ Procurement Transplant Network) database for all transplants conducted from 1987 to 2006. We identified 194 probable identical twin transplantations based on age, gender, race, ethnic category, blood type and HLA match. We evaluated the use of various immunosuppressive agents at discharge, 6 months and 1, 2 and 3 years after transplantation. Seventy-one percent of these patients at discharge and 34% at the end of 1 year were on immunosuppression. At discharge 61% received steroids and 30% received calcineurin inhibitors and 66% of these remained on calcineurin inhibitors at 1 year. Renal function was superior among those not maintained on immunosuppression. Thus, monozygotic transplantation confers an immunologic advantage that allows immunosuppression elimination despite a risk of recurrent glomerular disease such as FSGS with appropriate evaluation and management.