Introduction: The field of public health is increasingly implementing initiatives intended to make policies, systems, and environments (PSEs) more supportive of healthy behaviors, even though the evidence for many of these strategies is only emerging. Our objective was 3-fold: 1) to describe evaluations of PSE-change programs in which the evaluators followed the steps of the Centers for Disease Control and Prevention's (CDC's) Framework for Program Evaluation in Public Health, 2) to share the resulting lessons learned, and 3) to assist future evaluators of PSE-change programs with their evaluation design decisions. Methods: Seven Prevention Research Centers (PRCs) applied CDC's framework to evaluate their own PSE-change initiatives. The PRCs followed each step of the framework: 1) engage stakeholders, 2) describe program, 3) focus evaluation design, 4) gather credible evidence, 5) justify conclusions, and 6) ensure use and share lessons learned. Results: Evaluation stakeholders represented a range of sectors, including public health departments, partner organizations, and community members. Public health departments were the primary stakeholders for 4 of the 7 evaluations. Four PRCs used logic models to describe the initiatives being evaluated. Their evaluations typically included both process and outcome questions and used mixed methods. Evaluation findings most commonly focused on contextual factors influencing change (process) and the adoption or implementation of PSE-change strategies (outcome). Evaluators shared lessons learned through various channels to reach local stakeholders and broader public health audiences. Conclusion: Framework for Program Evaluation in Public Health is applicable to evaluations of PSE-change initiatives. Using this framework to guide such evaluations builds practice-based evidence for strategies that are increasingly being used to promote healthful behaviors.