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Context: Sub-Saharan Africa faces an increasing incidence and prevalence of life-limiting and life-threatening conditions. These conditions are associated with a significant burden of pain linked to high morbidity and disability that is poorly assessed and undertreated. Barriers to effective pain management partly relate to lack of access to opioid analgesia and challenges in their administration., Objectives: To identify country-specific and broader regional barriers to access, as well as the administration of opioids, and generate recommendations for advancing pain management in Southern Africa., Methods: A parallel mixed methods design was used across three countries: Mozambique, Swaziland, and Zimbabwe. Three activities were undertaken: 1) a review of regulatory and policy documentation, 2) group interviews, and 3) a self-administered key informant survey., Results: Barriers to accessing opioid analgesics for medical use include overly restrictive controlled medicines' laws; use of stigmatizing language in key documents; inaccurate actual opioid consumption estimation practices; knowledge gaps in the distribution, storage, and prescription of opioids; critical shortage of prescribers; and high out-of-pocket financial expenditures for patients against a backdrop of high levels of poverty., Conclusion: Policies and relevant laws should be updated to ensure that the legislative environment supports opioid access for pain management. Action plans for improving pain treatment for patients suffering from HIV or non-communicable diseases should address barriers at the different levels of the supply chain that involve policymakers, administrators, and service providers., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)