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Summary: Objective: To estimate the burden of HIV neurocognitive impairment (NCI) among adult patients on and off antiretroviral therapy (ART) in Sub-Saharan Africa. Methods: Estimates were derived from a random effects meta-analysis of prospective studies reporting HIV status, utilization of ART, and the presence of NCI determined using the International HIV Dementia Scale. Results: Sixteen studies with quality data from seven countries in Sub-Saharan Africa up to June 2012 were included. Among HIV patients, the frequency of NCI pre-ART was 42.37% (95% confidence interval (CI) 32.18–52.56%), and among those on ART for ≥6 months was 30.39% (95% CI 13.17–47.61%). Respective NCI estimates in studies from Uganda were 46.49% (95% CI 30.62–62.37%) and 28.50% (95% CI −1.31–58.30%). NCI was more common among patients with a concomitant psychiatric ailment. HIV-positive patients compared to HIV-negative controls were predisposed to NCI (odds ratio (OR) 6.49, 95% CI 1.68–25.08); the estimated unadjusted attributable risk of HIV infection leading to NCI was 85%. Meta-regression showed no associations between age, gender, CD4 cell counts, or years of education with NCI. Patients on ART were less likely to have NCI compared to HIV-infected pre-ART patients, with OR 0.36 (95% CI 0.19–0.69). In longitudinal studies with the same patients followed before and at ≥6 months after ART, the OR of NCI after ART compared to pre-ART was 0.23 (95% CI 0.14–0.37). The combined burden of NCI among pre-ART and on-ART patients in Sub-Saharan Africa was estimated at 8 121 910 (95% CI 5 772 140–10 471 680). No publication bias was observed, although residual confounding from differing environmental factors, stages of HIV infection, and viral clades might be a limitation. Conclusions: HIV strongly predisposes to NCI leading to a huge burden in Sub-Saharan Africa, and scale-up of ART can substantially reduce it. [ABSTRACT FROM AUTHOR]