Background. Studies on HIV-associated central nervous system (CNS) diseases in Cameroon are rare. The aim of this study was to describe the clinical presentation, identify aetiological factors, and determine predictors of mortality in HIV patients with CNS disease. Methods. From January 1, 2004 and December 31, 2009, we did at the Douala General Hospital a clinical case note review of 672 admitted adult (age ≥ 18 years) HIV-1 patients, and 44.6% (300/672) of whom were diagnosed and treated for HIV-associated CNS disease. Results. The mean age of the study population was 38.1 ± 13.5 years, and median CD4 count was 49 cells/mm(3) (interquartile range (QR): 17-90). The most common clinical presentations were headache (83%), focal signs (40.6%), and fever (37.7%). Toxoplasma encephalitis and cryptococcal meningitis were the leading aetiologies of HIV-associated CNS disease in 32.3% and 25% of patients, respectively. Overall mortality was 49%. Primary central nervous system lymphoma (PCNSL) and bacterial meningitis had the highest case fatality rates of 100% followed by tuberculous meningitis (79.8%). Low CD4 count was an independent predictor of fatality (AOR: 3.2, 95%CI: 2.0-5.2). Conclusions. HIV-associated CNS disease is common in Douala. CNS symptoms in HIV patients need urgent investigation because of their association with diseases of high case fatality.