We present a young immunocompetent male with diagnosed sputum culture-positive tuberculosis on intensive phase with observed daily four-drug antituberculosis therapy. He presented at 1-month of treatment with sequential bilateral pneumothoraces, increase in cavitation and consolidation and respiratory failure. Repeat smears for acid-fast bacilli had downgraded, and cultures were negative. Quantiferon-GOLD (initially negative) was now strongly positive. A diagnosis of possible immune reconstitution syndrome was considered and 0.25 mg/kg/day oral steroids administered. We also discuss an approach to differential diagnosis of a patient worsening on treatment for microbiologically confirmed tuberculosis in this manuscript.