INTRODUCTION: Drug induced liver injury (DILI) is a common cause of hepatotoxicity and around 15-20% of cases are attributed to herbal and drug supplements (HDS). Echinacea is a commonly used herbal supplement for treatment and prevention of common colds. We present a case of acute hepatitis secondary to Echinacea. CASE DESCRIPTION/METHODS: A 28-year-old Hispanic male with history of alcohol abuse. He was enrolled in an AA program and his last drink was about 18 months prior to presentation. He came to the ED complaining of weakness, nausea, postprandial vomiting, epigastric pain, and jaundice for 10 days. He denied taking medications, however, he started to take Echinacea supplements 1 month ago. Physical exam was only notable for jaundice and mild epigastric tenderness. Initial labs showed elevated AST at 1893 U/L, ALT 2763 U/L, ALP 191 U/L, T. Bili 10.4 mg/dL, D. Bili 8.32 mg/dL, GGT 141 U/L, and LDH 435 U/L. INR 1.07. UDS, Ethanol, acetaminophen, RPR, viral panel (including hepatitis A, B, C, E, CMV, EBV, HSV and HIV), autoimmune panel (including ANA, ASMA, AMA, LKM, SLA, P-ANCA), Ceruloplasmin, alpha-1-antitrypsin and HFE gene were all negative. Ultrasound of Abdomen revealed mild splenomegaly as well as thickening and edema of the gallbladder wall. CT abdomen showed periportal edema and thickening of the gallbladder wall. Vascular duplex of the abdomen was negative for thrombus. He was started on NAC infusion. His mental status and INR remained intact. Liver enzymes and bilirubin continued to rise. Liver biopsy showed panacinar cholestatic hepatitis consistent with adverse drug reaction. The patient was then transferred to a transplant center where he improved with supportive care. DISCUSSION: HDS are commonly used and often not disclosed to healthcare professionals resulting in diagnostic dilemmas. These supplements can lead to idiosyncratic liver injury with unexpected outcomes. Since it’s a diagnosis of exclusion, a comprehensive workup must be performed. There are only a few cases of echinacea induced hepatitis described in the literature. In some reports, autoimmune markers were positive suggesting drug induced autoimmune hepatitis but this does not apply to our patient. For non-paracetamol DILI, there is no strong evidence regarding benefit of NAC. However, due minimal side effect profile, it is widely used. Clinicians must maintain a high level of suspicion when encountering acute hepatitis with unclear etiology. A detailed history of medication and HDS use may hold the answer.