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Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa.Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM.Four hundred ninety nine participants were enrolled; 422 (84.6%) were HIV infected. In microbiologically confirmed TB patients, the LAM test was positive in 114 of 193 [sensitivity 59%, (95% confidence interval: 52 to 66)], including 112 of 167 [67% (59 to 74)] who were HIV infected. Among individuals classified as “not TB”, the LAM test was negative in 117 of 122 [specificity 96% (91 to 99)], including 83 of 88 [94% (87 to 98)] who were HIV infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82 of 193, P < 0.001) and detected 56% (62 of 111) of those who were sputum smear negative. HIV infection [adjusted odds ratio (AOR 13.4)], mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test.The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.