OBJECTIVE: To test if Mycobacterium tuberculosis screening results differ among patients with inflammatory disease depending on whether the QuantiFeron TB-Gold test (QFT) or tuberculin skin test (TST) is used; and to evaluate if a possible difference is influenced by the presence of risk factors or immunosuppression. METHODS: The interferon-gamma response to in vitro stimulation of M. tuberculosis-specific antigens was measured with QFT and results were compared with TST. Associations to bacillus Calmette-Guerin (BCG) vaccination, risk factors, and immunosuppression were analyzed for both tests. RESULTS: QFT and TST results were available for 294/302 and 241/302 patients, respectively; 234 had results from both tests. Twenty-one (7%) tested positive with QFT and 45 (19%) with TST. A positive QFT was associated with risk factors for M. tuberculosis infection: i.e., birth or upbringing in a TB-endemic area [risk ratio (RR) = 7.8, 95% CI 1.5-18.2, p < 0.001], previous TB treatment (RR 4.7, 95% CI 1.6-13.5, p = 0.005), and any latent TB infection risk factor (RR 4.7, 95% CI 2.1-11.0, p = 0.0002). Treatment with corticosteroids increased the risk for an inconclusive QFT result (RR 4.2, 95% CI 1.6-10.7, p = 0.04) and decreased the risk for a positive TST result (RR 0.4, 95% CI 0.1-1.0, p = 0.04). Agreement between the tests was low (kappa 0.2, 95% CI 0.02-0.3, p = 0.002). CONCLUSION: The study documented a high degree of discordant positive QFT and TST results. A positive QFT was more closely associated with risk factors for M. tuberculosis infection than the TST. The use of corticosteroids affected test outcome by increasing the risk for an inconclusive QFT result and decreasing the risk for a positive TST result.