Objectives: To compare quantiferon-TB gold "in tube" (QFT-IT) with the conventional tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) in HIV-infected adults in a setting highly endemic for tuberculosis with BCG vaccinated population in Bangalore, Karnataka, India. Patients and Methods: The study population (100 BCG-vaccinated adults) was divided into 4 groups: HIV patients with TB patient contact, HIV patients with past history of TB, TB patients (positive control), and healthy volunteers (negative control). Results: Overall agreement between TST and QFT-IT was 52.4% ( = 0.22). Increasing the TST cutoff value from 5 mm to 10 mm among HIV-positive groups resulted in better agreement 62.5% in Group 1 and 81.2% in Group 2. Discussion: In a setting with high TB prevalence, the TST gives increased false positives in HIV-positive groups if 5 mm is used as the cutoff value. This could be minimized by increasing the cutoff to 10 mm. Conclusion: The 2-step approach (initial testing of all cases with TST and confirmation of only those positive in TST by testing with QFT-IT) will be economical and help in treating LTBI cases in lower middle income countries like India.