We compared the tuberculin skin test (TST) to QuantiFERON-TB (QFT) and QuantiFERON-TB Gold (QFT-G) for the detection of latent tuberculosis. The QFT-G uses synthesized early secretory antigenic target 6 and culture filtrate protein 10 peptide antigens instead of purified protein derivative (PPD) antigens. The study included 137 adults in 3 groups: 1 (n = 81), at low risk for Mycobacterium tuberculosis (TB) and not vaccinated for Mycobacterium bovis bacillus Calmette-Guérin (BCG); 2 (n = 30), probably had TB exposure and were BCG vaccinated; and 3 (n = 26), at low risk for TB, not BCG vaccinated, but previously had a positive TST result. Positive results were as follows: group 1: TST 3 (3.7%); QFT 9 (11.1%); and QFT-G, 0 (0.0%); group 2: TST 26 (86.7%); QFT, 15 (50.0%); and QFT-G, 5 (16. 7%); and group 3: TST, 26 (100.0%); QFT, 13 (50.0%); and QFT-G, 9 (34.6%). The QFT-G demonstrated less cross-reactivity with BCG antigen and was more specific than QFT and TST in low-risk individuals.