Allogeneic hematopoietic cell transplantation (HCT) effectively treats seeveral non-malignant disorders (NMD) such as selected lysosomal disorders, cerebral adrenoleukodystrophy, and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with NMD who underwent a second allogenic HCT for GF using a non-myeloablative (NMA), low dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated peripheral blood stem cells. Median age at time of second HCT was 6.6 years (1.1 – 14.6 years). Fourteen of seventeen patients (82%) achieved engraftment, with a 3-year overall survival of 82% (95% CI, 54–94%). Day 100 transplant related mortality was 12% (95% CI, 0–27%). CMV and adenovirus reactivation occurred in 30% and fungal infections in 18%. The incidence of grade II-IV acute graft-versus-host disease was 35% (95% CI, 13–58%) with only 6% grade III-IV (95% CI, 0–17%). In summary, we illustrate excellent overall survival and acceptable toxicity using a NMA conditioning regimen for second HCT as salvage therapy for first graft failure in patients with non-malignant conditions.