Rifampicin is a key component of multidrug regimens not only for tuberculosis, but also nontuberculous mycobacterial infections (NTM) which are on the rise worldwide. Knowledge of the toxicity profile is important. Hepatotoxicity is a well-known side effect of Rifampicin necessitating regular liver function monitoring during therapy. Acute kidney injury (AKI) is a relatively rare complication, usually resulting from allergic interstitial nephritis (AIN). Rifampicin-induced intravascular hemolysis resulting in hemoglobinuria and AKI is even more uncommon, especially in Western countries with low prevalence of mycobacterial infections. Rifampicin-induced antibodies are implicated and this complication preferentially occurs during intermittent drug treatment protocols or when Rifampicin is restarted after a long drug-free interval. Awareness of this drug complication and its unique timing is important especially among emergency room physicians where patients with AKI may first present. It is equally important for nephrologists and pathologists. We describe one such case with detailed clinical course of the patient and interesting biopsy findings of ATN with intratubular hemoglobin casts.