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Introduction: Academic health centers are poised to improve health through their clinical, education, and research missions. However, these missions often operate in silos. The authors explored stakeholder perspectives at diverse institutions to understand challenges and identify alignment strategies. Methods: Authors used an exploratory qualitative design and thematic analysis approach with data obtained from electronic surveys sent to participants at five U.S. academic health centers (2017‐18), with four different types of medical school/health system partnerships. Participants included educators, researchers, system leaders, administrators, clinical providers, resident/fellow physicians, and students. Investigators coded data using constant comparative analysis, met regularly to reconcile uncertainties, and collapsed/combined categories. Results: Of 175 participants invited, 113 completed the survey (65%). Three results categories were identified. First, five higher‐order themes emerged related to aligning missions, including (a) shared vision and strategies, (b) alignment of strategy with community needs, (c) tension of economic drivers, (d) coproduction of knowledge, and (e) unifying set of concepts spanning all missions. Second, strategies for each mission were identified, including education (new competencies, instructional methods, recruitment), research (shifting agenda, developing partnerships, operations), and clinical operations (delivery models, focus on patient factors/needs, value‐based care, well‐being). Lastly, strategies for integrating each dyadic mission pair, including research‐education, clinical operations education, and research‐clinical operations, were identified. Conclusions: Academic health centers are at a crossroads in regard to identity and alignment across the tripartite missions. The study's results provide pragmatic strategies to advance the tripartite missions and lead necessary change for improved patient health. [ABSTRACT FROM AUTHOR]