We report on a boy with beta-thalassemia major who developed early graft failure after double-unit unrelated cord blood transplantation, who subsequently received a myeloablative preconditioning regimen using non-T-cell-depleted PBSCT from his HLA-haploidentical 2-loci-mismatched mother. Neutrophil recovery with full donor chimerism was observed at post-transplantation day +11. Furthermore, GVHD was easy to control. The patient was transfusion-independent with complete donor chimerism eight months post-transplant. The result indicated that fetomaternal microchimerism may be an important attribute of a successful transplant. We suggested that a third allo-HSCT may be taken into consideration for patients with transfusion-dependent thalassemia who experience graft failure, even after two previous transplants.