Drug hypersensitivity syndrome (DHS) has rarely been reported in association with vancomycin treatment. Here, we describe an 11-year-old girl who developed fever and a maculopapular rash on day 18 of intravenous vancomycin for treatment of infective endocarditis. The patient presented with fever, a maculopapular skin rash, hepatitis, and acute renal failure caused by vancomycin-induced DHS. The symptoms resolved in less than 24 h after withdrawal of vancomycin and treatment with corticosteroids. We present this case of DHS associated with vancomycin.