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Objectives: Interest is increasing in collaborations between public health and primary care to address the health of a community. Although the understanding of how these collaborations work is growing, little is known about the barriers facing these partners at the local level. The objective of this study was to identify barriers to collaboration between primary care and public health at the local level in 4 states., Methods: The study team, which comprised 12 representatives of Practice-Based Research Networks (networks of practitioners interested in conducting research in practice-based settings), identified 40 key informants from the public health and primary care fields in Colorado, Minnesota, Washington State, and Wisconsin. The key informants participated in standardized, semistructured telephone interviews with 8 study team members in 2014 and 2015. Interviews were audio recorded and transcribed verbatim. We analyzed key themes and subthemes by drawing on grounded theory., Results: Primary care and public health participants identified similar barriers to collaboration. Barriers at the institutional level included the challenges of the primary care environment, in which providers feel overwhelmed and resources are tight; the need for systems change; a lack of partnership; and geographic challenges. Barriers to collaboration included mutual awareness, communication, data sharing, capacity, lack of resources, and prioritization of resources., Conclusions: Some barriers to collaboration (eg, changes to health care billing, demands on provider time) require systems change to overcome, whereas others (eg, a lack of shared priorities and mutual awareness) could be addressed through educational approaches, without adding resources or making a systemic change. Overcoming these common barriers may lead to more effective collaboration.