Despite proven good efficacy of pneumococcal conjugated vaccine in preventing invasive pneumococcal disease, breakthrough infections remain a noticeable problem with significant morbidity and mortality, especially in selected high-risk groups. We present a 2-year-old girl with infantile spasm, who was treated with antiepileptic drugs and adrenocorticotropic hormone (ACTH). Vaccination with three doses 7-valent pneumococcal conjugate vaccine had been completed one month before ACTH therapy. Two months after ACTH therapy, she suffered from fever, cough, and decreased activity. Streptococcus pneumoniae, serotype 6B, was detected in blood culture. Vaccine failure could be possibly due to ACTH therapy. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.