Complex health care interventions involve multiple distinct elements that contribute to their functioning. Conducting systematic reviews of complex interventions has substantial challenges. Although methodological guidance exists, less is known about the practical strategies and approaches undertaken by systematic review groups to navigate common challenges and enhance impacts of systematic review findings. Objectives: Describe pragmatic approaches taken by Department of Veterans Affairs Evidence Synthesis Programs (VA ESP) in conducting systematic reviews of effectiveness and implementation barriers and facilitators for complex interventions to provide VA stakeholders with evidence to guide national health care practice and policy. Results: We describe 3 systematic reviews conducted by VA ESP teams to evaluate the evidence for complex health care interventions. We summarize key findings, implications for future research needs and policy, dissemination of findings, and approaches taken to address common challenges. The VA ESP experience adds to existing systematic review methods and provides a perspective on generating rigorous and relevant reviews of complex interventions. Conclusions: Reviews of complex interventions often encounter challenges related to sources of variability in many dimensions, and lack of clarity and information in reporting of intervention elements, local context, and implementation factors. Evidence synthesis teams should work closely with stakeholders to understand their needs, synthesize and interpret results in meaningful ways, and explore implications that are most relevant for day-to-day clinical practice and operational decisions of learning health care systems. More evaluation of the impact of systematic reviews may improve uptake of findings from future reviews and enhance translation of evidence into practice and policy.