ObjectivesWorldwide the use of opioids, both doctor-prescribed and illicit, has increased. In most countries, opioids are first prescribed by general practitioners (GPs). Identifying factors that influence GPs’ opioid prescription decision-making may help reduce opioid misuse and overuse. We performed a systematic review to gain insight into GP attitudes towards opioid prescription and to identify possible solutions to promote changes in the field of primary care.Design and settingSystematic review of qualitative studies reporting GPs’ attitudes towards opioid use in non-cancer pain management.MethodsWe searched Embase, Medline, Web of Science Core Collection, Cochrane, PsychInfo, Cumulative Index to Nursing & Allied Health Literature (CINAHL) and Google Scholar. Two independent reviewers selected studies based on prespecified eligibility criteria. Study quality was evaluated with the Critical Appraisal Skills Programme checklist, and their results were analysed using thematic analysis. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation—Confidence in the Evidence from Reviews of Qualitative research approach.ResultsWe included 14 studies. Four themes were established using thematic analyses: (1) GPs caught in the middle of ‘the opioid crisis’; (2) Are opioids always bad? (3) GPs’ weighing scale, taking patient-related and therapeutic relationship-related factors into account; and (4) GPs’ sense of powerlessness—lack of alternatives, support by specialists and lack of time in justifying non-prescriptions.ConclusionGP attitudes towards opioid prescribing for non-cancer pain are subject to several GP-related, patient-related and therapeutic relationship-related factors. Raising GP and patient awareness on the inefficacy of opioids in chronic non-cancer pain management and providing non-opioid alternatives to treat chronic pain might help to promote opioid reduction in primary care. More research is needed to develop practical guidelines on appropriate opioid prescribing, tapering off opioid use and adopting effective communication strategies.PROSPERO registration numberCRD42020194561.Cite Now