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Cryptococcal meningitis and tuberculosis are leading causes of mortality in patients initiating antiretroviral therapy in Africa. We hypothesized that a history of tuberculosis may predispose to the development of cryptococcal meningitis and examined the association using multivariate logistic regression in a cohort of patients initiating antiretroviral therapy. History of pulmonary tuberculosis was independently associated with the development of cryptococcal meningitis (odds ratio = 6.6; 95% confidence interval = 1.3–32.7) after adjustment for covariates, including CD4 cell counts. A number of potential mechanisms may underlie this association.