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Study objective: In 2003, the Institute of Medicine Committee on the Future of Emergency Care in the United States Health System convened and identified a crisis in emergency care in the United States, including a need to enhance the research base for emergency care. As a result, the National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. The objectives of these discussions were to identify key research questions essential to advancing the scientific underpinnings of emergency care and to discuss the barriers and best means to advance research by exploring the role of research networks and collaboration between the NIH and the emergency care community. Methods: The Medical-Surgical Research Roundtable was convened on April 30 to May 1, 2009. Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. After the conference, the lists were circulated among the participants and revised to reach a consensus. Results: Emergency care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype and genotype of patients manifesting a specific disease process and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency care research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical illnesses and injuries, and the development of treatments capable of halting or reversing them; the need for novel animal models; and the need to understand why there are regional differences in outcome for the same disease processes. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. The science of emergency care may be advanced by facilitating the following: (1) training emergency care investigators with research training programs; (2) developing emergency care clinical research networks; (3) integrating emergency care research into Clinical and Translational Science Awards; (4) developing emergency care–specific initiatives within the existing structure of NIH institutes and centers; (5) involving emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small, clinical trials; and (7) performing research to address ethical and regulatory issues. Conclusion: Enhancing the research base supporting the care of medical and surgical emergencies will require progress in specific mechanistic, translational, and clinical domains; effective collaboration of academic investigators across traditional clinical and scientific boundaries; federal support of research in high-priority areas; and overcoming limitations in available infrastructure, research training, and access to patient populations. [Copyright &y& Elsevier]