Objective. To measure the prevalence, severity and morbidity of neuropathic pain in AIDS patients, prior to the initiation of antiretroviral (ARV) therapy.Design. A prospective, cross-sectional and descriptive-analytical study.Setting. The Kalafong Hospital HIV Clinic in Pretoria.Subjects. All patients with confirmed AIDS who were referred to the Kalafong HIV clinic to be initiated on ARV therapy during the period August 2006 to March 2007.Outcome measures. Data were collected regarding the presence and severity of neuropathic pain in each subject. Pain of predominantly neuropathic origin (POPNO) was identified using the Neuropathic Pain Diagnostic Questionnaire (DN4). Numerical rating scales (NRS), adapted from the Brief Pain Inventory, were used to measure pain severity and pain-related interference with six aspects of daily living.Results. Of the 354 patients studied, 20.9% (95% confidence interval (CI) 16.8 - 25.2%) had POPNO. This pain was significantly more frequent in patients who were male, had lower CD4+ counts or higher viral load levels, and those on TB treatment. Eighty per cent of patients with POPNO experienced significant pain (worst pain severity ≥ 5 out of 10 on a NRS). Pain-related interference was highest for enjoyment of life, mood and ability to work. There was a significant positive correlation between severity of pain and pain-related interference for all domains of daily living evaluated.Conclusions. POPNO results in significant suffering and impaired functioning in patients with AIDS. It is therefore imperative that clinicians assess patients with AIDS for the presence and severity of neuropathic pain and manage it, using the most recent evidence-based guidelines.