Streptococcus pneumoniae isolates causing invasive disease at a large tertiary institute in Singapore from 2000 to 2007 were serotyped, with 84 (43.8 %) and 159 (82.8 %) isolates belonging to serotypes covered by the pneumococcal heptavalent conjugate and polysaccharide vaccines, respectively. All non-meningitis isolates were susceptible to penicillin, and the attributable mortality was 21.4 %. Patients who fulfilled the US Advisory Committee on Immunization Practices criteria for vaccination with the pneumococcal polysaccharide vaccine comprised 74.0 % of the study cohort and had a significantly higher mortality risk.