Statewide respiratory syncytial virus (RSV) lower respiratory tract infection hospitalization data of Colorado children with congenital malformations was used to estimate the population-based risk and severity of disease of RSV hospitalizations. Spina bifida without anencephaly, cleft palate, lung agenesis or dysgenesis, and biliary atresia were associated with a higher risk of being hospitalized with RSV lower respiratory tract infection and an increased severity of disease when hospitalized.