BACKGROUND: Respiratory syncytial virus (RSV) is a common, contagious, and seasonal pathogen causing 64 million acute respiratory infections annually in adults and children worldwide. High-risk adults, including older adults and those with cardiopulmonary conditions or weakened immune systems, are more likely to be infected. However, limited information exists on RSV incidence and associated costs among adults, including high-risk patients. OBJECTIVE: To evaluate the annual incidence of medically attended, International Classification of Diseases (ICD)-coded RSV among commercially insured adults and assess health care costs among adults with ICD-coded RSV in the United States. METHODS: Optum's deidentified Clinformatics Data Mart Database (January 01, 2007, to June 30, 2020) and IBM's MarketScan Databases (January 01, 2000, to July 31, 2020) were used. Medically attended, ICD-coded RSV incidence among adults was assessed from July 1 of a given year to June 30 of the next year and reported per 100,000 population. Trends in all-cause mean weekly costs pre-RSV and post-RSV diagnosis were reported. Results were reported overall and among patients aged 60-64 years, 65 years or older, 85 years or older, and 18-59 years at high risk of severe RSV (defined as having cardiopulmonary conditions or a weakened immune system). RESULTS: Annual incidence of medically attended, ICD-coded RSV in adults overall was 22.0-52.9 in Optum and 23.4-63.6 in MarketScan. Incidence rates were higher among patients aged 60-64 years (Optum: 25.2-66.1; MarketScan: 31.9-82.1), 65 years or older (Optum: 37.3-75.5; MarketScan: 54.1-97.3), 85 years or older (Optum: 92.4-140.6; MarketScan: 79.4-234.7), and 18-59 years at high risk of severe RSV (Optum: 41.3-135.9; MarketScan: 46.3-112.4). Mean weekly costs increased during the week before (Optum: $2,325; MarketScan: $2,080) and post-RSV diagnosis (Optum: $9,523; MarketScan: $3,551), compared with those in weeks 2-8 pre-RSV diagnosis (Optum: $1,350; MarketScan: $872). The increases in mean weekly costs during the week before and the week following RSV diagnosis were higher among patients aged 60-64 years (mean weekly costs in weeks 2-8 pre-RSV, week 1 pre-RSV, week 1 post-RSV; Optum: $1,623, $2,690, $10,823; MarketScan: $1,259, $2,992, $5,069), 65 years or older (Optum: $1,731, $3,067, $12,866; MarketScan: $1,517, $3,571, $5,268), 85 years or older (Optum: $1,563, $2,430, $18,134; MarketScan: $1,613, $4,113, $6,231), and 18-59 years at high risk of severe RSV (only for MarketScan: $1,237, $3,294, $5,531; costs were similar for Optum). CONCLUSIONS: Incidence of medically attended, ICD-coded RSV in adults was 22.0-63.6 per 100,000 population, a likely underestimation since RSV was not systematically tested and only RSV-coded cases were observed. Incremental costs associated with RSV were substantial. Incidence rates and costs were higher among patients aged 60 years or older and patients at high risk of severe RSV. DISCLOSURES: This study was sponsored by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of results, manuscript preparation, and publication decisions. B. Brookhart and D. Anderson are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. C. Rossi, B. Emond, J. Wang, P. Lefebvre, and M.-H. Lafeuille are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript. M. Mesa-Frias. and S. Drummond are former employees of Janssen Scientific Affairs, LLC. L. Lamerato is an employee of Henry Ford Health System and received research funding from Janssen Scientific Affairs, LLC.