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Background  The number of Americans who use tobacco has decreased in the twenty-first century, but electronic nicotine delivery systems (ENDS) have increased the complexity of treating tobacco dependence. The experiences of 18 family medicine practices were explored and opportunities to improve ENDS cessation were co-created in this study.    Methods  Eighteen family medicine practices were enrolled into an implementation project to incorporate ENDS cessation into their practice. The participants’ experiences were explored throughout the project using an iterative qualitative approach. The research team provided technical assistance. Semi-structured group interviews and focus groups were held with participants at the beginning, middle, and end of the project to explore participants’ experiences. The collective knowledge and experiences of participants, expert consultants and the research team were fused together to co-create opportunities to improve ENDS cessation.    Results  Nine opportunities to improve ENDS cessation were identified in three larger categories. The first category was leading change. This included: creating a vision for change to establish buy-in from key stakeholders and educate health care professionals to improve their confidence to address ENDS. The second category was creating processes. This included: establishing criteria for screening and quality improvement for ENDS cessation; being specific when asking about ENDS; creating electronic health record systems to support incorporating ENDS cessation; using chart audits if electronic health records cannot support incorporating ENDS into tobacco cessation; and assigning roles and responsibilities to members of the clinical care team. The third category was assisting patients who use ENDS. This included: educating patients and their parents/caregivers about ENDS and their potential harms, avoiding dual use, and developing a plan to quit.    Conclusions  This study highlights challenges and opportunities for incorporating ENDS cessation into family medicine. The opportunities outlined here provide a practical approach which is rooted in the experiences of family physicians and their clinical care teams working to improve how they address ENDS and based on peer reviewed literature and expert input. Improving how ENDS are addressed in family medicine will require more than clinical expertise. It will also require leadership skills and the ability to create process improvements.    Trial registration  Not applicable    Supplementary Information  The online version contains supplementary material available at 10.1186/s12875-021-01520-x.

Co-creating opportunities to incorporate cessation for electronic nicotine delivery systems in family medicine – a qualitative program evaluation