BACKGROUND: There is an increasing expectation for research to involve patient stakeholders. Yet little guidance exists regarding patient-engaged research in evidence synthesis. Embedded in a learning health care system, the Veteran Affairs Evidence Synthesis Program (ESP) provides an ideal environment for exploring patient-engaged research in a program of evidence synthesis. OBJECTIVE: The objective of this study was to explore views, barriers, resources, and perceived values of engaging patient advisors in a national program of evidence synthesis research. METHODS: We conducted 10 qualitative interviews with ESP researchers and 2 focus groups with patient stakeholder informants. We queried for challenges to patient involvement, resources needed to overcome barriers, and perceived values of patient engagement. We analyzed qualitative data using applied thematic and matrix techniques. RESULTS: Patient stakeholders and researchers expressed positive views on the potential role for patient engagement in the Veteran Affairs ESP. Possible contributions included topic prioritization, translating findings for lay audiences, and identifying clinically important outcomes relevant to patients. There were numerous barriers to patient involvement, which were more commonly noted by ESP researchers than by patient stakeholders. Although informants were able to articulate multiple values, we found a lack of clarity around measurable outcomes of patient involvement in systematic reviews. CONCLUSIONS: The research community increasingly seeks patient input. There are many perceived and actual barriers to seeking robust patient engagement in systematic reviews. This study outlines emerging practices that other evidence synthesis programs should consider, such as the careful selection of stakeholders; codeveloped expectations and goals; and adequate training and appropriate resources to ensure meaningful engagement.