To assess the diagnostic validity of laboratory cerebrospinal fluid (CSF) parameters for discriminating between tuberculous meningitis (TBM) and other causes of meningeal syndrome in high tuberculosis incidence settings. From November 2009 to November 2011, we included patients with a clinical suspicion of meningitis attending two hospitals in Lima, Peru. Using a composite reference standard, we classified them as definite TBM, probable TBM, and non-TBM cases. We assessed the validity of four CSF parameters, in isolation and in different combinations, for diagnosing TBM: adenosine deaminase activity (ADA), protein level, glucose level, and lymphocytic pleocytosis. One hundred and fifty-seven patients were included; 59 had a final diagnosis of TBM (18 confirmed and 41 probable). ADA was the best performing parameter. It attained a specificity of 95%, a positive likelihood ratio of 10.7, and an area under the receiver operating characteristics curve of 82.1%, but had a low sensitivity (55%). None of the combinations of CSF parameters achieved a fair performance for ‘ruling out’ TBM. Finding CSF ADA greater than 6 U/l in patients with a meningeal syndrome strongly supports a diagnosis of TBM and permits the commencement of anti-tuberculous treatment.