Background: The RE-AIM framework has been widely used in health research but it is unclear the extent to which this framework is also used for planning and evaluating health-related programs in clinical and community settings. Our objective was to evaluate how RE-AIM is used in the "real-world" and identify opportunities for improving use outside of research contexts. Methods: We used purposive and snowball sampling to identify clinical and community health programs that used RE-AIM for planning and/or evaluation. Recruitment methods included surveys with email follow-up to funders, implementers, and RE-AIM working group members. We identified 17 programs and conducted structured in-depth interviews with key informants (n = 18). Across RE-AIM dimensions, respondents described motivations, uses, and measures; rated understandability and usefulness; discussed benefits and challenges, strategies to overcome challenges, and resources used. We used descriptive statistics for quantitative ratings, and content analysis for qualitative data. Results: Program content areas included chronic disease management and prevention, healthy aging, mental health, or multiple, often behavioral health-related topics. During planning, most programs considered reach (n = 9), adoption (n = 11), and implementation (n = 12) while effectiveness (n = 7) and maintenance (n = 6) were considered less frequently. In contrast, most programs evaluated all RE-AIM dimensions, ranging from 13 programs assessing maintenance to 15 programs assessing implementation and effectiveness. On five-point scales, all RE-AIM dimensions were rated as easy to understand (Overall M = 4.7 ± 0.5), but obtaining data was rated as somewhat challenging (Overall M = 3.4 ± 0.9). Implementation was the most frequently used dimension to inform program design (M = 4.7 ± 0.6) relative to the other dimensions (3.0-3.9). All dimensions were considered similarly important for decision-making (average M = 4.1 ± 1.4), with the exception of maintenance (M = 3.4 ± 1.7). Qualitative corresponded to the quantitative findings in that RE-AIM was reported to be a practical, easy to understand, and well-established implementation science framework. Challenges included understanding differences among RE-AIM dimensions and data acquisition. Valuable resources included the RE-AIM website and collaborating with an expert. Discussion: RE-AIM is an efficient framework for planning and evaluation of clinical and community-based projects. It provides structure to systematically evaluate health program impact. Programs found planning for and assessing maintenance difficult, providing opportunities for further refinement.