Abstract Context Although pain and burdensome symptoms among HIV-infected persons can be effectively managed, the availability of opioids and other symptom-controlling drugs is a particular challenge in sub-Saharan Africa. Objectives This study aimed to identify current drug availability and prescribing practices in 12 sub-Saharan African countries and to examine the barriers and potential facilitators for use of opioids and other key HIV/AIDS symptom-controlling drugs. Methods This was a cross-sectional survey, integrating data from palliative care facilities and competent authorities within ministries of health in 12 African countries. Results Of 62 responding facilities, problems were reported in accessing named nonopioids, with a small number of facilities unable to dispense them. Less than half the facilities were currently prescribing opioids of any strength. Further problems were identified in terms of the availability and supply continuity of named antiemetics and anxiolytics. The data identified a number of systemic problems, suggesting that opioid supply issues are similar to less controlled drugs, such as antiemetics. Among competent authorities, there was no agreement on whether further opioid expansion was possible. Integration of data from care facilities and competent authorities highlighted a disparity in the understanding of the availability of specific drugs, with competent authorities naming drugs that were not listed by any responding facility in their respective country. Conclusion This study shows that opioid expansion needs to balance supply and skills: Currently there are insufficient trained clinical personnel to prescribe, and supply is unreliable. Efforts to expand supply should ensure that they do not weaken current systems.