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Research in critical care extends from the bench to the bedside, involving multiple departments, specialties, and funding organizations. Because of this diversity, it has been difficult for all stakeholders to collectively identify challenges and establish priorities.To define a comprehensive agenda for critical care research using input from a broad range of stakeholders to serve as a blueprint for future initiatives.The Critical Care Societies Collaborative (CCSC), consisting of the leadership of the American Association of Critical-Care Nurses (AACN), the American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Society of Critical Care Medicine (SCCM), joined the US Critical Illness and Injury Trials Group (USCIITG) in forming a task force to define a comprehensive critical care research agenda. This group of 25 identified experts was divided into subgroups to address basic, translational, clinical, implementation, and educational research. The subgroups met via conference calls, and the entire task force met in person for a 2-day session. The result was a detailed discussion of the research priorities that served as the basis for this report.The task force identified challenges, specific priority areas, and recommendations for process improvements to support critical care research. Additionally, four overarching themes emerged: 1) the traditional “silo-ed” approach to critical care research is counterproductive and should be modified; 2) an approach that more effectively links areas of research (ie, basic and translational research, or clinical research and implementation) should be embraced; 3) future approaches to human research should account for disease complexity and patient heterogeneity; and 4) an enhanced infrastructure for critical care research is essential for future success.This document contains the themes/recommendations developed by a large, multiprofessional cross section of critical care scientists, clinicians, and educators. It provides a unique framework for future research in critical care medicine.