Introduction: Distributing take-home naloxone (THN) kits from Emergency Departments (EDs) is an important strategy for preventing opioid overdose deaths. However, there is a lack of clear operational guidance for implementing ED-based THN programs. This scoping review had two objectives: 1) identify key strategies for THN distribution in EDs, and 2) develop a theory-informed implementation model that can be used to optimize the effectiveness of ED-based THN programs. Methods: We systematically searched health science databases through April 18, 2019. The search strategy combined terms representing the ED, naloxone, and take-home kits/bystander administration. Two reviewers independently screened the search results. We included all peer-reviewed articles that described THN distribution within EDs. A standardized form was used for data extraction. Included studies were coded by two reviewers and mapped to domains of the Consolidated Framework for Implementation Research (CFIR). A third reviewer with content expertise adjudicated disagreements in record screening and data coding. Results: Database searching retrieved 717 records after duplicates were removed. 87 full-text studies were assessed for eligibility. Two studies were added through other sources, resulting in a total of 21 studies included in the final review. Of note, 14 studies evaluated existing ED-based THN programs. We synthesized themes that emerged within each CFIR domain and identified four key implementation strategies: 1) develop ED policies on opioid harm reduction; 2) collaborate with community and government partners to ensure programs meet patient needs; 3) address provider attitudes and knowledge gaps through dedicated training; and 4) establish guidelines to identify patients who are at risk of opioid overdose, and engage at-risk patients to maximize THN acceptance. Conclusion: ED-based THN programs must be tailored to local community needs and available hospital resources. Innovative implementation strategies are needed to promote ED provider engagement, and reduce barriers to patient acceptance of THN in the ED. This scoping review highlights key considerations for ED-THN implementation that can guide EDs to establish new programs, or refine existing programs to maximize their effectiveness.