Evidence from formal evaluation of real-world practice can address gaps in the public health knowledge base and provide information about feasible, relevant strategies for varied settings. Interest in evaluability assessment (EA) as an approach for generating practice-based evidence has grown. EA has been central to several structured assessment processes that identify and select promising programs and evaluate those most likely to produce useful findings. The Emory Prevention Research Center used EA as part of an initiative to generate practice-based evidence for cancer prevention in southwest Georgia. Our initiative consisted of five steps: (1) environmental scan to identify potential programs, (2) program selection, (3) EA, (4) evaluation, and (5) dissemination. We identified nine programs, four of which completed a formal application, and conducted two EAs. EAs consisted of document review, site visits, and literature reviews. The EA purpose was to assess the program model, data availability, stakeholder interest in evaluation, feasibility of an outcome evaluation, and potential contribution to the literature. We conducted one outcome evaluation and one descriptive qualitative study; both were published in peer-reviewed journals. The outcome evaluation addressed knowledge gaps about strategies to promote colorectal cancer screening. Results led to the program’s inclusion in national resources for practitioners seeking evidence-based practices and helped the community organization expand and strengthen the program. As part of a structured assessment process, EA can identify programs most likely to produce useful results for dissemination and is a viable approach for local initiatives to generate practice-based evidence in rural or low-resource settings.