The QuantiFERON-TB Gold In-Tube method (QFT-GIT; Cellestis, Carnegie, Australia) is a recently US Food and Drug Administration-approved interferon-gamma release assay (IGRA) for the detection of tuberculosis infection, which has been screened for by the tuberculin skin test (TST) for nearly a century. We report a pilot study comparing the QFT-GIT and TST results for screening health care workers (HCWs) at Berkshire Medical Center (BMC; Pittsfield, MA), the second hospital in Massachusetts to use QFT-GIT. For the study, 40 BMC HCWs, 20 TST+ and 20 TST-, were screened with the QFT-GIT test. All 20 TST- subjects were also QFT-GIT-, while only 10 of 20 TST+ subjects were QFT-GIT+. The overall agreement between the QFT-GIT and TST results was 75% (kappa = 0.5; 95% confidence interval, 0.268-0.732). The suboptimal agreement was partially due to a higher specificity of QFT-GIT. Confounding factors (eg, bacille Calmette-Guérin vaccination status and birthplace) are discussed, and literature regarding IGRAs and their comparison with TST is reviewed.