The elderly suffer the majority of influenza hospitalizations and deaths and are a priority for determining influenza vaccine effectiveness (VE). The Univ. of Pittsburgh and UPMC Health System (UPMC) are located in Allegheny County (AC), in which influenza is reportable & which has one of the 5 oldest populations in the U.S. We propose a test-negative case-control study of influenza VE in 2 UPMC hospitals to determine VE against hospitalizations of adults. UPMC has been on the US News honor roll for over a decade, including "most wired" and has a strong research tradition. The influenza season will be determined from syndromic surveillance from multiple hospital EDs, the Health Dept. (ACHD), & from lab data from >14,000 respiratory viral panels (RVP) done annually at UPMC. Theradoc informatics will identify adult inpatients who have had an RVP conducted. Enrollees' survey data will be directly entered into NIH's REDCap. Frailty can be assessed by survey and/or electronic medical record (EMR) data (e.g., Charleson Co-morbidity Index) to assess confounders and effect modifiers. Our Data Center manages REDCap data, EMR data from hospitalizations, & immunization data for uploading to CDC. Population-based incidence of influenza hospitalizations will be determined from ACHD and UPMC St. Margaret hospitalization data and by agent-based modeling at the Pittsburgh Supercomputing Center. Our team is a strong candidate for this project because: 1) UPMC is the dominant regional health system with a strong bond rating; 2) infection control personnel recommend RVPs to establish diagnoses, and our team's leadership responsibilities at the hospitals can further influence the use of RVPs; 3) we have published data showing excellent concordance between UPMC's GenMark RVP and the CDC's PCR for detecting influenza; 4) research shows better protection in the elderly from high-dose influenza (HD) vaccine; UPMC has recommended and promoted HD vaccine in large quantities, although regular vaccine is available, allowing for vaccine type comparisons; 5) UPMC's EMR links inpatient and outpatient vaccination records, and interfaces with the state immunization registry; 6) it includes diverse, well-published investigators who have worked together previously.