BackgroundEmergency Departments (ED) staff, including nurses and physicians, are most directly involved in the care of people who use unregulated substances, and are ideally positioned to provide harm reduction interventions. Conceptualizing the ED as a complex adaptive system, this paper examines how ED staff experience opioid-specific harm reduction provision and engage in harm reduction practice, including potential facilitators and barriers to engagement.MethodsUsing a mixed methods approach, ED nurses and physicians completed a self-administered staff survey (n = 99) and one-on-one semi-structured interviews (n = 15). Five additional interviews were completed with clinical leaders. Survey data were analyzed to generate descriptive statistics and to compute scale scores. De-identified interview data were analyzed using a reflexive thematic analysis approach, which was informed by the theory of complex adaptive systems, as well as understandings of harm reduction as both a technical solution and a contextualized social practice. The final analysis involved mixed analysis through integrating both quantitative and qualitative data to generate overarching analytical themes.ResultsStudy findings illustrated that, within the context of the ED as a complex adaptive system, three interrelated contextual factors shape the capacity of staff to engage in harm reduction practice, and to implement the full range of opioid-specific harm reduction interventions available. These factors include opportunities to leverage benefits afforded by working collaboratively with colleagues, adequate preparation through receiving the necessary education and training, and support in helping patients establish connections for ongoing care.ConclusionsThere is a need for harm reduction provision across all health and social care settings where people who use unregulated opioids access public sector services. In the context of the ED, attention to contextual factors including teamwork, preparedness, and connections is warranted to support that ED staff engage in harm reduction practice.