Background: Tuberculosis is one of the deadliest diseases over the world. Diagnosis of pulmonary TB depends on combination various parameters. IGRA measure T cell release of IFN-γ in response to M.TB antigen. WHO policy statement as on IGRA use in low and middle income countries is not established yet. Objective: The present study aimed to compare between tuberculin skin test (TST) and interferon gamma release assay (IGRA) in the diagnosis of active tuberculosis infection and study the effect of 3 months of first line anti-TB therapy on the positivity of the IGRA test. Methods: 40 Egyptian patients were included in the study, and assigned as two groups; Group I comprised 20 patients with negative sputum for AFB by Ziehl-Neelsen stains with positive sputum culture for M.TB and Group II included 20 patients with positive sputum and Ziehl-Neelsen for AFB before and after 3 months of first line of anti-TB therapy. All patients were subjected to full history taking, clinical examination, X-ray chest, lab investigations, ESR measurements, microbiological tests and ELISA measurement of Quantiferon-TB Gold. Results: Lower significant values were found in group II after treatment than before treatment regarding clinical parameters and 1 st and 2 nd hours ESR. IGRA test and TST showed sensitivity (91.18%, 76.4%), specificity (83.33%, 66.67%), positive predictive value (96.88%, 92.86%), negative predictive value (62.5%, 33.3%) and accuracy of (90%, 75%) respectively. IGRA results had no statistical significant differences between the studied groups with poor agreement with TST ((κ) = 0.025). Conclusion: IGRAS test had high sensitivity and specificity in diagnosis of active TB. More studies are needed to evaluate the effect of anti-TB therapy on IGRA level.