The Federal Coordinating Council for Comparative Effectiveness Research (CER) was created under the American Recovery and Reinvestment Act (ARRA) of 2009 to coordinate comparative effectiveness research across the federal government. The ARRA provides $1.1 billion for CER, distributed across the Agency for Healthcare Research and Quality, the National Institutes of Health and the Office of the Secretary of Health and Human Services. The funds are designated to support, conduct and synthesize research involving the comparative effectiveness of health care treatments, as well as to encourage the development of clinical registries and electronic health data for use in generating comparative outcomes data. As these studies are conducted by the government, there will be safety data generated in this CER. With FDA becoming increasingly focused on safety signals through its Critical Path and Sentinel Initiatives, evaluation of CER data is likely to reveal additional safety signals with products studied that were not observed in pivotal trial populations. As additional product risks are identified, label updates and the possibility of REMS imposition will follow. Other downstream effects of CER will be reevaluating promotional materials in light of new safety data and signals, determining what competitive use, if any, may be made of comparative effectiveness data and grappling with the presentation of CER data so as not to suggest government endorsement of certain treatments. As the government begins to conduct or support CER, FDA and industry will be forced to grapple with the implications of these data sets.