▪Historically, outcomes after alternative donor (AD)-HCT for FA have been strikingly inferior to those observed in recipients of HLA-matched sibling donor (MSD) hematopoietic stem cells (HSC) with excessive rates of graft failure, graft-versus-host-disease (GVHD), regimen related toxicity and infection, resulting in poor survival rates. Between 2006-2013, 44 FA patients with marrow aplasia and good organ function underwent AD-HCT after total body irradiation 300 cGy (single fraction) with thymic shielding, fludarabine (FLU) 140 mg/m2, cyclophosphamide (CY) 40 mg/kg and antithymocyte globulin (ATG). Outcomes were compared to those transplanted with HSC from an HLA matched sibling donor (n=24) after FLU 175 mg/m2, CY 20 mg/kg and ATG conditioning (1999-2013). GVHD preventative measures were identical with all recipients of marrow having the graft T cell depleted by CD34 selection (regardless of donor type) prior to infusion in addition to cyclosporine A and methylprednisolone or mycophenolate mofetil. Recipients of umbilical cord blood had no additional graft processing.Except for higher use of pre-HCT G-CSF in recipients of AD-HCT, patient characteristics were similar between the 2 groups. Probabilities of neutrophil recovery, acute and chronic GVHD were similar between the groups (Table 1). Most notably, probability of survival at 3 years was the same between the two groups (Figure 1). [Display omitted] To our knowledge, this is the first demonstration of comparable outcomes after AD-HCT and MSD HCT for FA patients with marrow aplasia. These findings have three important implications: 1) timing for HCT need not be delayed if the patient lacks an HLA matched sibling donor, 2) potentially reduced enthusiasm for in vitro fertilization and preimplantation genetic diagnosis to have a 'savior sibling' and 3) ineligibility of FA young patients with a suitable AD (HLA matched adult volunteer or 5-6/6 matched UCB) and good organ function for high risk trials, including gene modified HSC. Disclosures:Wagner:Novartis: Research Funding.