Patient health outcomes improve when learning health care systems use evidence to implement promising services and allocate resources effectively. Here, we examine the unique environment in which Veterans Health Administration (VHA) leadership use evidence and the facilitators and barriers to using evidence synthesis products in decision-making. We end by describing the steps researchers can take to better support the needs of health system leadership. Methods: We conducted 20 semistructured phone interviews with individuals in VHA leadership positions. We used an inductive approach to identify themes observed across key informant interviews. Results: Key informants identified several factors that fostered the use of evidence including, timeliness, lack of bias, flexible approaches, and concise reports with a clear bottom line. Barriers included lack of relevant evidence and lack of information on how to translate evidence into practice, resistance to change among providers and within the larger health system, and political pressures to implement therapies or technologies with little evidence or uncertainty. Researchers can foster evidence uptake by developing a review scope and key questions that are important to multiple stakeholders, including frontline clinicians and health system leadership. Conclusions: The VHA’s evidence needs resemble other health systems, but evidence synthesis products should include a translational component to enhance implementation. Resistance to change and political pressures can further hinder the uptake of evidence within VHA.