BACKGROUND: Epilepsy affects nearly 50 million people worldwide. Self-management is critical for individuals with epilepsy in order to maintain optimal physical, cognitive, and emotional health. Implementing and adopting a self-management program requires considering many factors at the person, program, and systems levels. We conducted a systematic review of qualitative and mixed-methods studies to identify facilitators and barriers that impact implementation and adoption of self-management programs for adults with epilepsy. METHODS: We used established systematic review methodologies for qualitative and mixed-methods studies. We included studies addressing facilitators (i.e., factors that aided) or barriers (i.e., factors that impeded) to implementation and adoption of self-management interventions for adults with epilepsy. We conducted a narrative thematic synthesis to identify facilitators and barriers. RESULTS: The literature search identified 2700 citations; 13 studies met eligibility criteria. Our synthesis identified five themes that categorize facilitators and barriers to successful implementation epilepsy self-management: (1) relevance, intervention content that facilitates acquisition of self-management skills; (2) personalization, intervention components that account for the individual's social, physical, and environmental characteristics; (3) intervention components, components and dosing of the intervention; (4) technology considerations, considerations that account for individual's use, familiarity with, and ownership of technology; and (5) clinician interventionist, role and preparation of the individual who leads intervention. We identified facilitators in 11 of the 13 studies and barriers in 11 of the 13 studies and classified these by social-ecological level (i.e., patient/caregiver, program, site/system). CONCLUSION: Identification of facilitators and barriers at multiple levels provides insight into disease-specific factors that influence implementation and adoption of self-management programs for individuals with epilepsy. Our findings indicate that involving individuals with epilepsy and their caregivers in intervention development, and then tailoring intervention content during the intervention, can help ensure the content is relevant to intervention participants. Our findings also indicate the role of the clinician (i.e., the individual who provides self-management education) is important to intervention implementation, and key issues with clinicians were identified as barriers and opportunities for improvement. Overall, our findings have practical value for those seeking to implement and adopt self-management interventions for epilepsy and other chronic illnesses. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number is CRD42018098604.