Background Most children with respiratory syncytial virus (RSV) infection have a self-limiting course that can be managed with supportive care, and hospitalization is uncommon. The objectives of this study were to evaluate the epidemiology, outcomes, associated comorbidities, and temporal trends in the prevalence of infants one to 24 months of age who required hospitalization for RSV infection in the United States of America from 1997 to 2019. Methods In this retrospective cross-sectional study, we utilized the Kids' Inpatient Database (KID) to investigate the prevalence and outcomes of RSV bronchiolitis within a large cohort of discharged patients from 1997 to 2019. We included children one to 24 months of age admitted with a diagnosis of RSV bronchiolitis. Neonates were excluded from the analysis. A chi-square for linear trend was used to analyze trends in the prevalence of RSV bronchiolitis hospitalization, the presence of complex chronic conditions (CCC), congenital heart disease (CHD), the use of non-invasive and invasive mechanical ventilation (NIV and IMV), and hospital mortality. Results There were a total of 566,786 infants aged one to 24 months hospitalized with RSV infection out of a total of 9,309,597 discharges during the eight-year cohort, with a hospital prevalence of 60.9 per 1000 discharges and a hospital mortality rate of 0.09% (95% confidence interval (CI): 0.08%-0.1%). There was no trend in hospitalization rates of RSV infections per 100,000 U.S. population during the study period, with a decrease in hospital mortality trend. Children with RSV bronchiolitis were more likely to have government insurance and reside in zip codes with the lowest income quartile. There was a significant seasonal and regional variation in RSV-related hospitalizations. The presence of CCC was identified in 2.4% of the RSV group compared to 5.1% of non-RSV discharges (odds ratio (OR): 0.46, 95% CI: 0.45-0.47; p<0.001). The prevalence of RSV among all discharges has significantly increased over the study period, rising from 51.6 cases per 1000 discharges in 1997 to 180.1 cases per 1000 discharges in 2019 (p<0.001). The prevalence of CCC and CHD among RSV patients has also shown an upward trend, with CCC cases increasing from 1,411 in 1997 to 2,795 in 2019 and CHD cases rising from 1,795 to 3,622 during the same period. The use of invasive mechanical ventilation, non-invasive ventilation, and extracorporeal membrane oxygenation has consistently increased over time. Additionally, complications such as the need for cardiopulmonary resuscitation have demonstrated a similar increasing trend, although they have remained overall low. However, population-based hospitalization rates showed no significant trend. Conclusions The hospitalization rates at a population level in the United States for RSV infection in children aged one to 24 months remained steady from 1997 to 2019, while hospital mortality rates showed a declining trend. There is an increased proportion of comorbid conditions and increased resource utilization in children with RSV. These findings are important for monitoring the effectiveness of preventive strategies for severe RSV infections.