Respiratory syncytial virus (RSV) is a significant cause of illness in elderly and high-risk adults, with a disease burden comparable to that of nonpandemic influenza A. This study evaluated RSV and influenza A infections in healthy elderly patients, high-risk adults, and hospitalized patients with acute cardiopulmonary conditions over four consecutive winters. RSV infection was identified in 102 patients in the prospective cohorts and 142 hospitalized patients, while influenza A was diagnosed in 44 and 154 patients, respectively. RSV infection occurred in 3-7% of healthy elderly patients and 4-10% of high-risk adults annually. In the hospitalized cohort, RSV and influenza A resulted in similar lengths of stay, intensive care use, and mortality rates. RSV accounted for 10.6% of hospitalizations for pneumonia, 11.4% for chronic obstructive pulmonary disease, 5.4% for congestive heart failure, and 7.2% for asthma. RSV infection generated fewer office visits than influenza in healthy elderly patients, but high-risk adults used healthcare services similarly. In the hospitalized group, RSV and influenza A had similar healthcare impacts. The study highlights the importance of RSV in elderly and high-risk populations and supports the development of an RSV vaccine. The findings suggest that an effective RSV vaccine could offer significant benefits for these groups.Respiratory syncytial virus (RSV) is a significant cause of illness in elderly and high-risk adults, with a disease burden comparable to that of nonpandemic influenza A. This study evaluated RSV and influenza A infections in healthy elderly patients, high-risk adults, and hospitalized patients with acute cardiopulmonary conditions over four consecutive winters. RSV infection was identified in 102 patients in the prospective cohorts and 142 hospitalized patients, while influenza A was diagnosed in 44 and 154 patients, respectively. RSV infection occurred in 3-7% of healthy elderly patients and 4-10% of high-risk adults annually. In the hospitalized cohort, RSV and influenza A resulted in similar lengths of stay, intensive care use, and mortality rates. RSV accounted for 10.6% of hospitalizations for pneumonia, 11.4% for chronic obstructive pulmonary disease, 5.4% for congestive heart failure, and 7.2% for asthma. RSV infection generated fewer office visits than influenza in healthy elderly patients, but high-risk adults used healthcare services similarly. In the hospitalized group, RSV and influenza A had similar healthcare impacts. The study highlights the importance of RSV in elderly and high-risk populations and supports the development of an RSV vaccine. The findings suggest that an effective RSV vaccine could offer significant benefits for these groups.