Hepatic toxicity caused by propafenone is extremely rare. We here describe a case of acute cholestasis secondary to propafenone treatment in an elderly male with no history of preexistent liver disease. The clinical picture and time course of the symptoms seem to be compatible with a direct toxic reaction. Age-related delays in hepatic drug metabolism should explain the hazardous increase in the bioavailability of this drug. Despite the rarity of this complication, propafenone should be considered as a potential cause of drug-induced cholestasis in elderly patients. The literature on the hepatotoxicity of propafenone is also reviewed.