Background: Tuberculosis has been declared the opportunistic infection in HIV-infected patients in many countries of the world. People with HIV are up to 50 times more likely to develop TB than HIV Negative people. However, the prevalence of HIV/AIDS and tuberculosis in Karachi city is unprecedented and the convergence of these two infectious diseases is increasingly and significantly endangering human health and hampering socioeconomic development. Objective: To determine the frequency & predisposing factors of HIV & co-infection with Tuberculosis in the metropolitan city of Karachi. Methodology: This comparative cross sectional study was conducted from September 2008 to April 2009 in 80 known HIV Positive Intravenous drug users. The data was obtained on the basis of standardized and structured questionnaire, which was later classified for demographic and predisposing factors for analysis by SPSS (version 20). Additionally, sputum test (Smear & Culture) was also performed to confirm TB. Results: Demographically, higher percentages of HIV patients were homeless, young (21-30 years), less educated, unemployed and 100% smokers. TB exposure, blood transfusion, Jail and illegal sexual contact were also documented. Out of 80 HIV, only 05 cases were found co-infected with tuberculosis. However, the statistical correlation between HIV and TB was significant. Conclusion: Occurrence of HIV/TB co-infection was poor but cannot be ignored since this cross sectional study having participant's limitations as well. As a follow up to the outcome of this study, the linkage and awareness of these two conditions, especially at community level is recommended.