Introduction: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. Methods: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identiﬁed using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was deﬁned as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the base-line period. Patients were categorized as initially hospitalized if hospitalized within 1 day of RSV diagnosis. Logistic regression models were developed to determine predictors of initial hospitalization. Healthcare utilization and costs for 180 days pre- and post-RSV diagnosis were compared. Results: The study included 756 HR patients who were initially hospitalized with RSV diagnoses. Among these, 61.7% were diagnosed in the emergency department vs 15.3% in a physician’s ofﬁce, with hypertension (76.3%), chronic obstructive pulmonary disease (COPD)(53.7%), and high cholesterol (52.0%) observed as the most prevalent comorbidities. Of these, COPD, congestive heart failure, chronic kidney disease, and previous evidence of pneumonia were signiﬁcant predictors of hospitalization. Other signiﬁcant predictors of hospitalization included older age, hematological malignancies, stroke, and baseline healthcare resource use. Among both HR and non-HR hospitalized patients, there was a signiﬁcant increase in healthcare resource utilization following hospitalization, including the number of inpatient admissions and longer hospital stays post-RSV diagnosis. The total mean all-cause healthcare costs among HR hospitalized patients increased by $9210 per patient (p \ 0.0001) post-RSV diagnosis. Conclusion: Hospitalized Medicare beneﬁciaries with RSV infections pose a signiﬁcant healthcare burden as compared with non-hospitalized patients, mainly driven by higher comorbidity, higher likelihood of multiple inpatient admissions, and costly medical interventions.