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Background To address escalating opioid-related harm, an Australian evidence-based guideline for deprescribing opioids was recently published. However, the barriers and enablers to its implementation remain unclear.Objective To explore insights of Australian primary care physicians, the target end-users of the guideline, on implementing opioid deprescribing recommendations in primary care.Methods This qualitative study employed individual in-depth semistructured interviews with a convenience and purposive sample of Australian primary care physicians from October 2023 to February 2024. The interview guide was informed by the ‘Theoretical Domains Framework (TDF)’ to identify and understand determinants of healthcare professional behaviour. All interviews were recorded, transcribed verbatim and analysed using qualitative content analysis. Transcripts were first inductively coded for familiarisation and then deductively coded to TDF domains to align participants’ responses with the chosen framework.Results Fourteen primary care physicians were interviewed, half of whom had more than 20 years of clinical experience. Three themes were identified, mapping to all 14 TDF domains. Theme 1, ‘I am trying to do the right thing’, encompassed the perception that primary care physicians generally did not self-identify deficiencies in their own knowledge, skills, abilities or willingness to implement opioid deprescribing guideline recommendations. Rather, they attributed implementation challenges to contextual (ie, patient, other healthcare professionals or system-related) barriers. Theme 2, ‘caught between “ideal” and “real”’, reflected primary care physicians’ recognition of the recommendations’ merit and their intent to implement them, but their feeling that the realities and complexities of practising in primary care hindered them from being able to do so. Theme 3, ‘shifting from reactive prescribing to proactive deprescribing’, encompassed strategies targeting communities, stakeholders (healthcare professionals and patients), governments and the healthcare system to drive meaningful change in pain management and opioid deprescribing in primary care.Conclusion Primary care physicians valued evidence-based guidance on opioid deprescribing but reported facing contextual barriers that hindered implementation of the guideline. Tailored strategies were seen as essential to enable a shift from reactive prescribing to proactive deprescribing to improve patient care.