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Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepa-totoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare. Till date, only 3 cases of ALF related to etodolac have been reported in the literature. Here we report two cases with a unique presentation of ALF occurring due to DILI caused by etodolac, as diagnosed by Roussel Uclaf Causality Assessment Method (RUCAM).