The quantitative interferon (IFN)-gamma in response to Mycobacterium tuberculosis-specific antigens declines in tuberculosis patients after starting treatment, however, in some cases remains high despite clinical improvements. Our aim was to evaluate clinical parameters associated with remaining QuantiFERON-TB Gold (QFT-G) positive after treatment.A prospective cohort study of 101 culture-positive, positive QFT-G, HIV-uninfected patients with pulmonary tuberculosis. QFT-G was performed at diagnosis, at the end of intensive phase, at treatment completion, and 5–7 months post-treatment completion.There were 80 patients with complete results, 34 (43%) remaining QFT-G positive and 46 (58%) reverting to QFT-G negative at the 5–7 month post-treatment time point. There was a significant decline in IFN-gamma levels in response to both CFP-10 and ESAT-6 with tuberculosis treatment. Multivariate analysis revealed significant associations between IFN-gamma levels detected before treatment and remaining QFT-G positive post-treatment after adjustment for smear status, presence of cavitation, and positive sputum culture two months after starting treatment.Quantitative QFT-G responses drop significantly in active tuberculosis patients undergoing treatment, with almost 60% becoming test negative. Reversion to a negative QFT-G result was closely associated with the magnitude of the IFN-gamma response prior to treatment and increasing age.