Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone. AIM: To evaluate the immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients. METHOD: 241 patients aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel index and the MiniMental State. Serotype-specific IgG was measured by ELISA at base line and 6 months after vaccination. Antibody responses were defined by the ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2-fold increase, acceptable > or = 2.0 to 3.99-fold and strong > or = 4.0-fold increase). RESULTS: Pre-immunization IgG was generally low and did not differ significantly by age or frailty. Post-immunization, IgG increased to all four serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for (18C). There was no significant difference between the two vaccine types (23PPV versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4. Although there was some variation by serotype, responses after vaccination were lowest in the most frail or aged subjects. CONCLUSIONS: Pneumococcal vaccines are perceived to offer low protection in the frail elderly, but our study showed that the proportion of this vulnerable population with acceptable responses is encouraging. Frailty, as measured by the Frailty Index, appears to be a better predictor of immune response to pneumococcal vaccines than age alone.