This study aims to determine the prevalence of Mycobacterium tuberculosis infection and its association with HIV and other health risk factors among drug users. A sample of 716 IDUs and crack users were enrolled from community sites. Consenting subjects were tested for HIV serum antibody status. Drug users with an unknown PPD status were administered a PPD skin test and an anergy panel of three antigens (Candida, mumps and tetanus). Overall, 68 (10.3%) were reactive to the PPD skin test, 240 (34.7%) were HIV positive and 195 (29.5%) showed cutaneous anergy. Participants infected with tuberculosis (TB) were more likely to be HIV seropositive, and to have a history of incarceration and residential drug treatment than those not infected. In addition, TB infection was more prevalent among intravenous drug users (IDUs) and shooting gallery managers. These findings suggest that drug users should be considered at high risk for TB and HIV infection. Innovative programs to monitor both infections among drug users are needed to arrest what can become a dual epidemic of HIV and TB in the near future.