Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts development of CM in antiretroviral (ART) naïve HIV-infected patients with severe immune depression. Systematic pre-ART CrAg screening and pre-emptive oral fluconazole is thus recommended. We postulated that a semi-quantitative CrAg screening approach could offer clinically relevant advantages. Methods: ART-naïve asymptomatic adult outpatients with <100 CD 4 cells/mm 3 presenting to the Yaoundé Central Hospital, Cameroon were screened for CrAg using the IMMY lateral flow assay (LFA). CrAg positive patients were consented for lumbar puncture and those with proven CM were treated with combination antifungal therapy and those with no CM were offered long-term oral fluconazole. Simultaneous on-site evaluation of CrAg detection using the new LFA Biosynex R CryptoPS test was performed and both tests were subsequently compared to a reference commercialized CrAg enzyme immunoassay (EIA). Results: Prevalence of serum CrAg in 186 screened adults was 7.5% (95%CI: 4.5– 12.4). In CrAg positive patients, CM prevalence was 45.5% (95%CI: 18.3–75.7). IMMY and Biosynex CryptoPS strongly agreed in serum, plasma, and cerebrospinal fluid (Kappa: 98.4, 99.5, 100%, respectively, p < 0.001), and disagreed in urine (29 isolated positive CrAg in urine with IMMY, none with Biosynex and none of whom had proven CM). Compared to EIA, serum specificities were 96.6 and 98.3%, respectively. With Biosynex CryptoPS, all CM patients were serum T2-band positive compared to none