Leah L Zullig,1,2 Hayden B Bosworth1–4 1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA; 2Department of Medicine, Duke University Medical Center, Durham, NC, USA; 3School of Nursing, 4Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Abstract: Practitioners and researchers often design behavioral programs that are effective for a specific population or problem. Despite their success in a controlled setting, relatively few programs are scaled up and implemented in health care systems. Planning for scale-up is a critical, yet often overlooked, element in the process of program design. Equally as important is understanding how to select a program that has already been developed, and adapt and implement the program to meet specific organizational goals. This adaptation and implementation requires attention to organizational goals, available resources, and program cost. We assert that translational behavioral medicine necessitates expanding successful programs beyond a stand-alone research study. This paper describes key factors to consider when selecting, adapting, and sustaining programs for scale-up in large health care systems and applies the Knowledge to Action (KTA) Framework to a case study, illustrating knowledge creation and an action cycle of implementation and evaluation activities. Keywords: program sustainability, diffusion of innovation, information dissemination, health services research, intervention studies