Background and Aims To compare tuberculin skin test (TST) and interferon gamma release assay (IGRA) in the screening of LTBI among patients with infammatory bowel disease (IBD) in an endemic area for tuberculosis, to evaluate the need for repeating tests during anti-TNFα, therapy, and to check whether the results may be afected by immunosuppression. Methods A cross-sectional study of 110 IBD patients and 64 controls was conducted in Rio de Janeiro, Brazil. The TST was administered after the Quantiferon(®)-TB Gold In-tube test was performed. Results TST and IGRA agreement was poor regarding diagnosis (kappa: control=0.318; UC=0.202; and CD=−0.093), anti-TNFα therapy (kappa: with anti-TNFα=0.150; w/o anti-TNFα=−0.123), and immunosuppressive therapy (IST) (kappa: with IS=−0.088; w/o IS=0.146). Indeterminate IGRA was reported in four CD patients on IST. Follow-up tests after antiTNFα identifed conversion in 8.62% using TST and 20.0% using IGRA. Considering IGRA as a criterion standard, TST showed low sensitivity (19.05%) and positive predictive value (PPV) (21.05%). LTBI detection remarkably improved when IGRA was added to TST (sensitivity of 80.95% and PPV of 53.13%). Results were particularly relevant among CD patients where rates started from zero to reach sensitivity and PPV of more than 60%. Conclusion IGRA alone was more efective to detect LTBI than TST alone and had an overall remarkable added value as an add-on sequential test, particularly in CD patients. While cost-efectiveness of these strategies remains to be evaluated, IGRA appears to be justifed in CD prior to and during anti-TNFα therapy, where tuberculosis is endemic.