Objective: Interferon-[gamma] release assays (IGRAs) are an important tool for detecting latent "Mycobacterium tuberculosis" infection (LTBI). Insufficient data exist about IGRA specificity in college health centers, most of which screen students for LTBI using the tuberculin skin test (TST). Participants: Students at a low-TB incidence college health center. Methods: TST and T-SPOT."TB" were performed on prospectively recruited students. TB exposure risk was assessed using a questionnaire: Those at low risk were assumed to not have LTBI in order to calculate test specificity. Results: Of 184 students enrolled, 143 had results available for both TST and T-SPOT."TB". Agreement of the tests was 97% (kappa statistic 0.717; 95% confidence interval, 0.399-1.00). Among 124 low-risk students, specificity for TST and T-SPOT."TB" were 98.4% and 100%, respectively. Conclusions: T-SPOT."TB" specificity was high among low-risk students. Additional studies such as cost-effectiveness analyses using T-SPOT."TB" as a single or confirmatory test to TST are needed to contribute to LTBI screening policy decisions. (Contains 1 table.)