Background Respiratory syncytial virus (RSV) infections are common in adults, but data describing the cost of RSV‐associated hospitalization are lacking due to inconsistency in diagnostic coding and incomplete case ascertainment. We evaluated costs of RSV‐associated hospitalization in adult patients with laboratory‐confirmed, community‐onset RSV. Methods We included adults ≥ 18 years of age admitted to three hospital systems in New York during two RSV seasons who were RSV‐positive by polymerase chain reaction (PCR) and had more than or equal to two acute respiratory infection symptoms or exacerbation of underlying cardiopulmonary disease. We ed costs from hospital finance systems or converted hospital charges to cost using cost‐charge ratios. We converted cost into 2020 US dollars and extrapolated to the United States. We used a generalized linear model to determine predictors of hospitalization cost, stratified by admission to intensive care units (ICU). Results Cost data were available for 79% (601/756) of eligible patients. The mean total cost of hospitalization was $8403 (CI95 $7240–$9741). The highest costs were those attributed to ICU services $7885 (CI95 $5877–$10,240), whereas the lowest were radiology $324 (CI95 $275–$376). Other than longer length of stay, predictors of higher cost included having chronic liver disease (odds ratio OR 1.38 CI95 1.05–1.80) for patients without ICU admission and antibiotic use (OR 1.49 CI95 1.10–2.03) for patients with ICU admission. The annual US cost was estimated to be $1.2 (CI95 0.9–1.4) billion. Conclusion The economic burden of RSV hospitalization of adults ≥ 18 years of age in the United States is substantial. RSV vaccine programs may be useful in reducing this economic burden.