OBJECTIVES: To prioritize research topics relevant to the care of the growing population of older adults with multiple chronic conditions (MCCs). DESIGN: Survey of experts in MCC practice, research, and policy. Topics were derived from white papers, funding announcements, or funded research projects relating to older adults with MCCs. SETTING: Survey conducted through the Health Care Systems Research Network (HCSRN) and Claude D. Pepper Older Americans Independence Centers (OAICs) Advancing Geriatrics Infrastructure and Network Growth Initiative, a joint endeavor of the HCSRN and OAICs. PARTICIPANTS: Individuals affiliated with the HCSRN or OAICs and national MCC experts, including individuals affiliated with funding agencies having MCC-related grant portfolios. MEASUREMENTS: A "top box" methodology was used, counting the number of respondents selecting the top response on a 5-point Likert scale and dividing by the total number of responses to calculate a top box percentage for each of 37 topics. RESULTS: The highest-ranked research topics relevant to the health and healthcare of older adults with MCCs were health-related quality of life in older adults with MCCs; development of assessment tools (to assess, e.g., symptom burden, quality of life, function); interactions between medications, disease processes, and health outcomes; disability; implementation of novel (and scalable) models of care; association between clusters of chronic conditions and clinical, financial, and social outcomes; role of caregivers; symptom burden; shared decision-making to enhance care planning; and tools to improve clinical decision-making. CONCLUSION: Study findings serve to inform the development of a comprehensive research agenda to address the challenges relating to the care of this "high-need, high-cost" population and the healthcare delivery systems responsible for serving it.