Cytomegalovirus (CMV) reactivation in CMV-seropositive patients after haploidentical T-cell receptor αβ+/CD19+ depleted hematopoietic cell transplant (HCT) is high. Due to delayed CMV-specific immune reconstitution, patients may require prolonged antiviral therapy including secondary prophylaxis (SP). Valganciclovir is preferred for SP, however, antiviral options for SP could be limited in the setting of resistant CMV. We report successful off-label use of letermovir for SP in a haploidentical TCRαβ+/CD19+ depleted pediatric HCT recipient with resistant CMV disease, its pharmacokinetic parameters, and dose titration based on area under time concentration curve.