Splenectomy predisposes for invasive pneumococcal disease. We investigated the immune response of splenectomised hereditary spherocytosis (HS) patients upon sequential pneumococcal vaccination. Thirty-nine HS-patients (2- to 18-year-old) had undergone near-total or total splenectomy. All received one dose of 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent-pneumococcal-polysaccharide vaccine (PPV-23) 2 months apart. Pneumococcal antibodies against serotypes 5/6B/7/14/18C/19F/23F and immunoglobulin serum concentrations were determined before PCV-7 and 4 weeks after PPV-23. Significant rises in antibody geometric mean concentrations were observed after PCV-7 except for serotypes 5 and 7, which increased after PPV-23. We found no impact of the mode of splenectomy.