Objective To compare outcomes of infants and children who underwent lung transplantation for genetic disorders of surfactant metabolism ( SFTPB , SFTPC , ABCA3 , and NKX2-1 ) over 2 epochs (1993-2003 and 2004-2015) at St Louis Children's Hospital. Study design We retrospectively reviewed clinical characteristics, mortality, and short- and long-term morbidities of infants (transplanted at <1 year; n = 28) and children (transplanted >1 year; n = 16) and compared outcomes by age at transplantation (infants vs children) and by epoch of transplantation. Results Infants underwent transplantation more frequently for surfactant protein-B deficiency, whereas children underwent transplantation more frequently for SFTPC mutations. Both infants and children underwent transplantation for ABCA3 deficiency. Compared with children, infants experienced shorter times from listing to transplantation ( P  = .014), were more likely to be mechanically ventilated at the time of transplantation ( P  < .0001), were less likely to develop bronchiolitis obliterans post-transplantation ( P  = .021), and were more likely to have speech and motor delays ( P  ≤ .0001). Despite advances in genetic diagnosis, immunosuppressive therapies, and supportive respiratory and nutritional therapies, mortality did not differ between infants and children ( P  = .076) or between epochs. Kaplan-Meier analyses demonstrated that children transplanted in epoch 1 (1993-2003) were more likely to develop systemic hypertension ( P  = .049) and less likely to develop post-transplantation lymphoproliferative disorder compared with children transplanted in epoch 2 (2004-2015) ( P  = .051). Conclusion Post-lung transplantation morbidities and mortality remain substantial for infants and children with genetic disorders of surfactant metabolism.