The ability of interferon-gamma release assays (IGRAs) to detect latent tuberculosis (TB) infection before liver transplantation (LT)is not well established. The aims of this study were (1) to compare the ability of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-IT) test (a whole-blood IGRA) to diagnose latent TB infections in patients awaiting LT and (2) to correlate the results with the severity of liver disease. We conducted a prospective, cross-sectional study of patients who were evaluated for LT between July 2008 and July 2010. The 95 patients who were included underwent the 2-step TST and the QFT-IT test. The mean Model for End-Stage Liver Disease (MELD) score was 13.8. Forty-four patients (46.3%) had positive TST results, 42 (44.2%) had positive QFT-IT results, and 2 (2.1%) had indeterminate QFT-IT results. Simultaneous TST and QFT-IT testing yielded a positivity rate of 55.8% [95% confidence interval (CI) = 45.3-65.9] with either test, and the 2-step TST yielded a positivity rate of 46.3% (95% CI = 36.1-56.8); the difference was 9.5% (P = 0.004). In an adjusted analysis, the rates for positive TST results were lower in patients with MELD scores > or = 18 [odds ratio (OR) = 0.2, 95% CI = 0.04-0.7], lower in Child-Pugh-Turcotte (CPT) class C patients versus CPT class A patients (OR = 0.1, 95% CI = 0.02-0.6), and higher in males (OR = 6.4, 95% CI = 1.9-22.0). In contrast, only being male (OR = 3.5, 95% CI = 1.1-11.0) was associated with positive QFT-IT results; no association was found with the MELD score (OR = 0.8, 95% CI = 0.2-2.8) or the CPT class (OR = 0.3; 0.05-1.4). In conclusion, the QFT-IT test is better than the TST for detecting latent TB infection in patients with more advanced liver disease. Our results support the regular use of the QFT-IT test for screening patients with end-stage liver disease for latent TB infection before LT.