Invasive pneumococcal disease (IPD) is of concern in Japan, where the heptavalent pneumococcal conjugate vaccine (PCV7) is unavailable. We determined serotypes, genotypes indicating β-lactam resistance, and antibiotic susceptibilities of 496 isolates from normally sterile sites in patients (193 children, 303 adults) from 186 institutions between August 2006 and July 2007. Disease presentations included sepsis (46·2%), pneumonia (31·5%), and meningitis (17·5%). Mortality was 1·4% in children and 22·1% in adults, many of whom had underlying diseases. In children, serotype 6B (22·5%) was followed by 19F (14·1%), and 14 (13·1%); potential coverages of PCV7 and PCV13 were 75·4% and 93·7%, respectively. In adults, serotype 12F (14·3%) was followed by 3 (11·3%), and 6B (10·3%); 23-valent polysaccharide vaccine (PPV23) coverage was 85·4%. Most serotype 12F strains were gPISP, with pbp2b gene alteration; carbapenem had an excellent MIC90. PCV7 is recommended for children and PPV23 for adults to increase prevention against IPD.