Summary Objective We aimed to investigate the prognosis of HIV-infected patients with acute neurological complications at the highly active antiretroviral therapy (HAART) era. Methods We performed a retrospective study in HIV-infected patients admitted to a medical ICU with neurological complications between 2001 and 2008. Results Among the 210 studied patients (median [interquartile range] CD4-cell count: 80 [18–254]/μL; HIV viral load: 4.8 [2–5.3] log 10/mL), 40 (19%) had unknown HIV status at admission. Neurological complications consisted in delirium (45%), coma (39%), seizures (32%) and/or intracranial hypertension (21%). Admission diagnoses were AIDS-defining CNS disease for 88 (42%) patients, non-AIDS-defining CNS disease for 45 (21%), and systemic disease with neurological signs for 77 (37%). Seizures ( p = 0.003), focal deficit ( p < 0.001) and intracranial hypertension ( p < 0.001) were more frequently observed in patients with AIDS-defining CNS disease. Factors independently associated with ICU mortality (29.5%) were intracranial hypertension [odds ratio (OR), 5.09; 95% confidence interval (95% CI), 2.17–11.91], vasopressor use [OR, 3.92; 95% CI, 1.78–8.60] and SAPS II score [per 10-point increment, OR, 1.59; 95% CI, 1.31–1.93]. Conclusions Prognosis of HIV-infected patients with neurological complications depends rather on clinical presentation than on HIV-related parameters. Intracranial hypertension symptoms at admission have a major impact on outcome.