The process of moving research insights into clinical practice can be slow and a gap often remains between best practices, frequently developed within single sites or small populations, and general practice delivered at a population scale. The field of implementation science seeks to mend this gap by promoting the adoption and appropriate use of effective interventions, practices, and programs, which includes the study of scale-up and spread of innovations. While hard-to-engage sites may have unique characteristics from sites that are engaged quickly or earlier, they are not typically differentiated in scale-up and spread processes. Thus, there is a lack of information about hard-to-engage sites and how to tailor approaches to these sites in scale-up and spread efforts. The objective of this project is to use systematic review and qualitative interview methods together to understand strategies available to scale up and spread clinical and administrative practices across large healthcare systems such as the VHA, with a focus on “hard-to-engage” sites.