Background: Fundamental to successfully translating evidence-based interventions to real life settings with diverse populations is achieving fidelity to the intervention within the given public health setting. Health departments may be key in addressing the obesity epidemic given their unique position to deliver obesity prevention services in community settings. We developed the Weight-Wise II Program from four evidenced-based interventions for implementation in local health departments. For this study, we conducted a process evaluation of the implementation of the Weight-Wise II Program, an intensive evidence-based behavioral weight loss program for low-income, mid-life women. Methods: The Weight-Wise II Program, a 16-week group-based weight loss program, was implemented in six local health departments. The RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) served as a guide to conduct a comprehensive process evaluation. Process data were collected and analyzed using quantitative and qualitative methods. Results: The Weight-Wise II Program reached low-income and mid-life women, a high-risk population, and was effective in achieving modest weight loss. Attendance and self-monitoring were positively associated with weight loss. Interventionists delivered the program as intended and it was well received by participants. Planned adaptations enhanced program implementation by being responsive to participant and health department needs. Despite implementation by health department staff, the program was not routinely maintained three years post-intervention. Conclusion: Evidence-based weight loss interventions can be successfully implemented in local health departments. RE-AIM is a useful framework for systematically evaluating the process of implementation and impact of a behavioral weight loss intervention offered in public health settings. The addition of complementary implementation frameworks may help in identification of contextual factors influencing subsequent maintenance of evidence-based interventions in public health settings. Trial registration: ClinicalTrials.gov Identifier: NCT01141348. Registered 9 June 2010 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01141348 Contributions to the literature The Weight-Wise II Program is an evidence-based weight loss intervention translated for implementation in local health departments serving a diverse low-income population. This study provides an approach and tools for comprehensively monitoring and evaluating evidenced-based programs implemented in public health settings. The study findings address gaps in the literature by providing guidance on program adaptations while maintaining fidelity including organizational contexts, participant engagement, and sustainability.