We present here the first published use of letermovir for the treatment of resistant cytomegalovirus (CMV) in a pediatric patient. A 14-year-old girl underwent a double unrelated umbilical cord blood transplantation to treat her sickle cell disease (hemoglobin SS) and developed ganciclovir-resistant CMV DNAemia with end-organ involvement that was treated successfully with a combination of foscarnet and letermovir. After she was transitioned to letermovir monotherapy for secondary prophylaxis, she developed recurrent DNAemia with laboratory-confirmed ganciclovir, foscarnet, and letermovir resistance. [ABSTRACT FROM AUTHOR]