© 2010, East African Medical Association. All rights reserved. Objectives: To determine the prevalence, clinical features, risk factors and outcomes associated with cryptococcal meningitis (CM) in human immunodeficiency virus (HIV) positive patients at two referral hospitals in Nairobi, Kenya. Design: Prospective, observational study. Setting: Kenyatta National Hospital (KNH) and Mbagathi District Hospital (MDH), Nairobi, Kenya Subjects: Three hundred and forty HIV patients presenting with suspected CM. Results: Of three hundred and forty suspected CM patients, 111 (33%) were diagnosed with CM by CrAg. Among CM patients, in-hospital mortality was 36% (38/106), median age was 35 years (range, 19-60 years) and median CD4 count was 41 cells/μL (n=89, range 2-720 cells/μL). Common clinical manifestations among CM patients included headache 103 (93%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with CM were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and current use of anti-retroviral therapy were associated with reduced risk for CM. Conclusions: There is a high prevalence of CM and CM-associated mortality in HIV patients at KNH and MDH despite treatment with antifungal and anti-retroviral drugs. This study demonstrates the need to address the existing inadequacies of CM patient outcomes in Kenya.