Umbilical cord blood (UCB) is used increasingly as a source of hematopoietic cells because of a lower risk of graft-versus-host disease (GVHD). Myeloablative conditioning before allogeneic umbilical cord blood transplant (allo-UCBT) results in thymic epithelial cell injury and T-cell immune deficiency. Full-term fetal blood cells were used as hematopoietic cells in a previous murine allo-UCBT model with a limited number of mice surviving the myeloablative conditioning. We designed a viable murine allo-UCBT protocol with platelet concentrate support. Keratinocyte growth factor (KGF) is a mitogen of thymic epithelial cells that promotes recovery of thymic epithelium when given before total body irradiation (TBI)-containing conditioning in experimental murine models. We hypothesized that KGF pre-administration would improve post-allo-UCBT thymopoiesis. To test this hypothesis, allo-UCBT recipient mice were given KGF or control saline prior to UCBT. Platelet concentrate support significantly improved the survival rate of murine allo-UCBT recipients. KGF administration significantly increased donor-derived T and natural killer T (NKT) cells at day +35 in spleens of allo-UCBT recipients. KGF administration also improved thymic function after allo-UCBT, resulting in higher copies of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in splenocytes. Finally, we found that KGF pre-administration could enhance the graft-versus-leukemia effect. In conclusion, KGF can be administered safely to recipients of allo-UCBT to enhance T-cell immune reconstitution.