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BackgroundLifestyle interventions that optimize nutrition, physical activity, sleep health, social connections, and stress management, and address substance use can reduce cardiometabolic risk. Despite substantial evidence that healthful plant-based diets are beneficial for long-term cardiometabolic health and longevity, uncertainty lies in how to implement plant-based lifestyle programs in traditional clinical settings, especially in safety-net contexts with finite resources.MethodsIn this mixed-methods implementation evaluation of the Plant-Based Lifestyle Medicine Program piloted in a large public healthcare system, we surveyed participants and conducted qualitative interviews and focus groups with stakeholders to assess program demand in the eligible population, and feasibility of implementation within the safety-net setting.FindingsProgram demand was high and exceeded capacity. Participants’ main motivations for joining the program included gaining more control over life, reducing medication, and losing weight. The program team, approach, and resources were successful facilitators. However, the program faced administrative and payor-related challenges within the safety-net setting, and participants reported barriers to access.ConclusionsStakeholders found the program to be valuable, despite challenges in program delivery and access. Findings provide guidance for replication. Future research should focus on randomized controlled trials to assess clinical outcomes as a result of program participation.