The epidemiology of extrapulmonary tuberculosis (TB) is not well understood. We studied all cases of extrapulmonary TB reported in San Francisco during 1991-2000 to determine risk factors for extrapulmonary TB and the proportion caused by recent infection. Isolates were analyzed by IS6110-based restriction fragment-length polymorphisms analysis. There were 480 cases of extrapulmonary TB, of which 363 (76%) were culture positive; isolates were genotyped for 301 cases (83%). Multivariate analysis identified young age, female sex, and HIV infection as independent risk factors for nonrespiratory TB (excluding pulmonary, pleural, and disseminated TB). Pleural TB was less common in HIV-seropositive persons and women than were nonrespiratory forms of extrapulmonary TB. Pleural TB is different from other forms of extrapulmonary TB and is associated with the highest clustering rate (35% of cases) of all forms of TB. This high rate of clustering occurs because pleural TB is often an early manifestation of recent infection.