Background: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) and hospitalizations in United States (US) infants and young children. Objective: Following ACIP’s recommendation for nirsevimab in infants up to 8 months, we conducted a systematic literature review (SLR) to describe RSV and LRTI epidemiology in US children aged ≥8 months to <5 years across healthcare settings. Methods: This SLR followed PRISMA guidelines and was pre-registered on PROSPERO (#CRD42024599190). Literature published from 2009-2024 were evaluated for outcomes including: RSV and LRTI rates in outpatient, urgent care, or emergency department (ED); RSV and LRTI hospitalization rates; and RSV laboratory testing practice and patterns. GraphPad Prism 10 for Mac was used for the data visualizations. Results: This review included 101 studies. The literature evidence comprised 34 prospective cohort, 62 retrospective cohort, and 5 studies of other designs (1 trial, 1 case-control, 3 cross-sectional surveys). Units for the rates were variable. They were expressed using person-time (e.g., per 1000 person-season, person-year) or as proportions without the time component. In the outpatient or ED settings, 8 studies reported RSV rates; in the outpatient clinics, RSV rates ranged 1.5 to 277.8 per 1000 children. In the ED, RSV rates ranged 10 to 84.6 per 1000 children. Bronchiolitis rates were available in one study each: 81 per 1000 and 15.9-19.8 per 1000 children in the outpatient and ED settings, respectively. In urgent care, no data were available. RSV and LRTI hospitalization rates were reported in 26 studies. Figures 2 and 3 report the age-stratified RSV and LRTI hospitalization rates (12-23 months of age or 24-59 months). For RSV and LRTI, the rates were variable. Data for age-stratified pneumonia or bronchiolitis rates were sparse compared to the RSV data. RSV laboratory testing patterns were reported in 7 studies with only 1 study (Bhat 2013; Table 1) providing outpatient data. Though limited, underestimation of RSV is indicated in the outpatient compared to the inpatient setting (testing rates: 69-77% vs. 70-100%, respectively; data not shown). Bhat 2013 was a prospective cohort study conducted in 2009 and based on data from the Indian Health Service. Conclusions: This systematic review underscores the impact of RSV in US children 8 months through <5 years of age in all healthcare settings. No data are available for urgent care and data from outpatient and ED settings remain limited while hospital data are variable. Inconsistent testing and reporting practices may be contributing factors as the data for bronchiolitis and pneumonia were sparse. Given the variable disease burden estimates, additional studies are essential to assess healthcare utilization and impacts in this population. Funding and COI Disclosures: This study was funded by Sanofi. EpidStrategies has received research funding from Sanofi for other studies.