Background <p>Few studies have systematically examined the barriers and facilitators to buprenorphine uptake, despite increasing opioid-related harms and guideline recommendations for use. The aim of the study was to use behaviour change frameworks to investigate barriers and facilitators to buprenorphine access and use from diverse perspectives in Ontario, Canada.</p> Methods <p>We conducted semi-structured face-to-face or telephone interviews with Ontarians including: people with living/lived expertise of opioid use (including family members), healthcare professionals, and organizational and system-level representatives. We used purposive sampling via existing professional networks to recruit participants with diverse experiences. The Theoretical Domains Framework (TDF) guided the data collection tool and analysis. Interviews were recorded, transcribed, coded, and underwent thematic analysis involving three study team members.</p> Results <p>We interviewed 28 participants between September 2019 and January 2020. Three predominant TDF domains were identified across all 4 levels: (1) environmental context/resources; (2) beliefs about consequences; (3) social influences. Key cross-cutting themes included access to comprehensive care, medication and treatment characteristics, confidence and experiences with buprenorphine, as well as supportive relationships and stigma/discrimination.</p> Conclusions <p>Multi-level barriers to optimal buprenorphine implementation continue in the face of the drug toxicity crisis. To counter the identified barriers and enhance facilitators, there is need for mentorship models of support for prescribing, flexibility in buprenorphine treatment requirements, better recognition of mental health and the social determinants of health in buprenorphine treatment, and comprehensive and integrated systems of care.</p>