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Respiratory syncytial virus (RSV) is the leading viral cause of death in infants younger than 1 year. In July 2014, the American Academy of Pediatrics (AAP) Committee on Infectious Diseases concluded that the “limited clinical benefit” for infants born at more than 29 weeks' gestation, together with the associated high cost of the immunoprophylaxis, no longer supported the routine use of palivizumab (Synagis).To evaluate the impact of the newly adopted AAP palivizumab prophylaxis administration on health and subsequent hospital costs of infants born between 29 and less than 32 weeks' gestation.A retrospective cohort analysis from a single institution across the duration of the study comparing the clinical and financial outcomes of infants (aged < 32 weeks) treated under the 2009 AAP guidelines (PRE) and infants (aged >29 weeks) managed after the 2014 AAP guidelines (POST) took effect.RSV-positive admissions were greater in the POST cohort versus the PRE cohort (P = .04). There were no readmission deaths due to RSV infection in either cohort. The number needed to treat to avoid a single RSV-positive hospitalization was 20 infants at an estimated palivizumab cost of $90,000 to avoid an estimated hospital cost of $29,000.Assessment of individual risk factors and their ability to predict severe RSV risk/disease, thus, would allow providers greater flexibility in determining need for prophylaxis therapy.Longitudinal evaluation of financial and clinical outcomes is needed to determine the impact of the 2014 AAP revised regulatory guidelines.