Haemophilus influenzae type b conjugate vaccine was recently introduced to Japan for voluntary immunizations. H. influenzae type b remains a leading cause of pediatric invasive diseases in Japan. The purposes of this study were to verify the suitability of the H. influenzae type b conjugate vaccine for immunizing children with a history of invasive H. influenzae type b disease and to determine whether H. influenzae type b conjugate vaccine is immunogenic in these children. The subjects comprised 64 children with a history of invasive H. influenzae type b disease. Serum samples from 64 patients with H. influenzae type b systemic infection in the acute and convalescent phases were analyzed. Serum anti-polyribosylribitol phosphate antibody responses of patients < 2 years old were poorer than those observed in patients ≥ 2 years old. Nineteen of the 64 patients received a single dose of H. influenzae serotype b conjugate vaccine, and then follow-up serum was taken and analyzed. Eighteen of 19 patients had ≥ 1 μg/mL of anti-polyribosylribitol phosphate antibody titer after the first dose of H. influenzae type b conjugate vaccine. H. influenzae type b conjugate vaccine is immunogenic in children with invasive H. influenzae type b disease. Children < 4 years old, and particularly < 2 years old, with invasive H. influenzae type b disease should receive subsequent immunization with a H. influenzae type b conjugate vaccine.