Patients with severe aplastic anemia who fail immunosuppressive therapy have a dismal prognosis. Hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is one of the most effective options. Two institutions have independently adopted a PTCy approach for patients undergoing HSCT from URD. Thirteen patients were included, 11 of which had been treated with immunosuppressive therapy. Most (8/13) had a mismatched URD. All patients were conditioned with fludarabine, cyclophosphamide and TBI in various dose combinations. PTCy was given in a dose of 100 mg/kg. Two patients died, and overall survival was 85% at 2 years. All patients engrafted but one developed secondary graft failure. Overall survival at 2 years was 85%. Of the eleven patients alive after 2 years, nine have complete donor chimerism. All surviving patients are transfusion independent. Ten (77%) patients had CMV reactivation, and two patients had more than one reactivation. No EBV reactivation or PTLD was observed. Four patients had mild hemorrhagic cystitis. In summary, we have shown that the PTCy is a promising approach for aplastic anemia in the URD setting.Copyright © 2020. Published by Elsevier Inc.