OBJECTIVES: Influenza virus activity increases hospitalizations for a broad range of cardiopulmonary diagnoses, including pneumonia and influenza (P&I). However, only a few economic studies have even partially incorporated broader respiratory (including P&I) and cardiovascular outcomes (R&C) in assessing vaccination effects. We developed a conceptual model that assessed the costs and benefits of vaccinating elderly individuals from a US societal perspective based on 2 different outcomes (P&I only vs. R&C). METHODS: A literature-based decision model was used to estimate the short- and long-term costs and quality-adjusted life expectancy (QALE) associated with annual influenza vaccination for the elderly population (aged³65 years, N=37,888,000). One version of the model included P&I outcomes only whereas the other version included the broader influenza-related R&C outcomes. The reduction rate of influenza due to vaccination was 30% and applied to the probability of seeking medical attention, antivirals and antibiotics utilization, and indirect costs. The reduction in hospitalization due to influenza was calibrated to reflect recent epidemiologic estimates. RESULTS: When only P&I were modeled, the number of hospitalizations was 63,000 and 88,000 with and without vaccination, respectively. The QALE per person was 7.7514 versus 7.7509 years; and the average cost per person was $118 versus $121, respectively. When R&C were modeled, the number of hospitalizations increased to 180,000 and 239,000; the QALE per person decreased to 7.7392 and 7.7355; and the average cost increased to $325 and $388, respectively, with and without vaccination. The inclusion of all R&C outcomes improved the estimated vaccination benefits, with more hospitalizations avoided (34,000), QALE gained (123,000 QALYs), and cost savings (>$2 billion). Results were similar in sensitivity analyses. CONCLUSIONS: Excluding R&C outcomes considerably underestimates the burden of influenza and the economic benefits of influenza vaccination. Future economic assessments of influenza vaccination strategies should include all R&C outcomes.