Lack of expansion of the deceased donor supply has resulted in a severe shortage of organs worldwide. Spousal donors are one possible alternative organ source for patients on the kidney transplant waiting list. Despite human lymphocyte antigen (HLA) matching between recipients and unrelated donors being poor, the reported survival rates for these grafts, including spouses, are comparable to those for grafts from living related donors and higher than those for deceased donor kidneys. In 2000, our renal transplantation program began accepting living donor-recipient pairs with one or zero HLA matches. The purpose of this study was to assess this policy for accepting living unrelated donors. The 3-year graft survival rates for the transplants from living unrelated donors were similar to that for transplants from living related donors (log-rank = 0.078). The number of HLA mismatches did not significantly influence the survival rates for either of these groups of living donor transplants. Multivariate analysis revealed that dialysis duration (P =.057) and recipient age (P =.066) negatively influenced patient survival in living donor kidney transplantation. The graft and patient survival rates for the donor transplantations were higher than those for deceased donor transplantations. In light of these findings and considering the increasing problem of organ shortage, we conclude that living unrelated kidney transplantation should be performed, with strict guidelines. Spousal donation is the most favorable form of living unrelated renal transplantation.