Two-step tuberculin testing and standardized interviews of 793 current and former drug users were performed to determine the risk factors for tuberculin positivity. The prevalence of tuberculin positivity was 25%. Factors independently associated with tuberculin positivity among participants seronegative for human immunodeficiency virus (HIV) included crack cocaine use (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.5), employment as a home health aide (adjusted OR, 2.1; 95% CI, 1.0-4.1), birth in Puerto Rico (adjusted OR, 2.2; 95% CI, 1.3-3.6), foreign birthplace (adjusted OR, 4.7; 95% CI, 1.6-13.6), African American race (adjusted OR, 2.5; 95% CI, 1.2-5.0), reported tuberculosis exposure (adjusted OR, 2.3; 95% CI, 1.2-4.4), and older age (adjusted OR, 2.9; 95% CI, 1.2-6.7). Additional risk factors among HIV-infected participants included alcoholism (adjusted OR, 2.4; 95% CI, 1.0-5.8) and high CD4(+) lymphocyte count. Identification of and administration of appropriate chemoprophylaxis to drug users with these risk factors should be given high priority.