Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARI) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARI, focusing on specific age groups, comorbidities, and demographic factors. Methods: A retrospective observational study was conducted using electronic medical records of adults aged ≥60 years hospitalized for ARI, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden. Results: RSV infections resulted in significantly higher direct costs compared to other ARI, particularly in patients aged 70-80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies. Conclusions: RSV poses a substantial economic and clinical bur-den on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vul-nerable population. These findings support the inclusion of RSV vaccines in immunization pro-grams, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.

The authors have declared no competing interest.

This research received no external funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of HM Hospitales (protocol code 24.04.2344-GHM and date of approval: 2024/05/08) for studies involving humans

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors