Clopidogrel is a thienopyridine derivative with a relatively low occurrence of adverse side effects. Increasing evidence, however, suggests that clopidogrel may cause severe liver injury. Until now, five cases of clopidogrel-induced acute hepatitis have been reported. We describe the case of an 80-year-old man who developed symptomatic liver disease 6 weeks after 1×75 mg/day clopidogrel intake as adjunctive antiplatelet therapy for a renal artery stent implantation. Histological examination revealed severe acute hepatitis with extensive hepatocanalicular cholestasis and focal cell necrosis with a preferential zone-3 distribution of hepatic damage. In the present paper, we describe the clinico-histopathological characteristics of a case of clopidogrel-induced acute hepatitis and discuss the current literature.