A three-month study (February to April 2010) of the National Aeronautics and Space Administration (NASA) Aviation Safety (AvSafe) program was conducted. This study comprised three components: (1) a statistical analysis of currently available civilian subsonic aircraft data from the National Transportation Safety Board (NTSB), the Federal Aviation Administration (FAA), and the Aviation Safety Information Analysis and Sharing (ASIAS) system to identify any significant or overlooked aviation safety issues; (2) a high-level qualitative identification of future safety risks, with an assessment of the potential impact of the NASA AvSafe research on the National Airspace System (NAS) based on these risks; and (3) a detailed, top-down analysis of the NASA AvSafe program using an established and peer-reviewed systems analysis methodology. The statistical analysis identified the top aviation “tall poles” based on NTSB accident and FAA incident data from 1997 to 2006. A separate examination of medical helicopter accidents in the United States was also conducted. Multiple external sources were used to develop a compilation of ten “tall poles” in future safety issues/risks. The top-down analysis of the AvSafe was conducted by using a modification of the Gibson methodology. Of the 17 challenging safety issues that were identified, 11 were directly addressed by the AvSafe program research portfolio.