OBJECTIVES Streptococcus pneumoniae infections in adults are associated with substantial morbidity, mortality, and costs. The objective of this study was to provide an analysis of the conclusions and assumptions of published studies on the cost-effectiveness of pneumococcal polysaccharide vaccination (PPV-23 (23 serotypes)) in adults. METHODS A search of recent literature (1997–2008) was conducted to identify cost-effectiveness studies pertaining to the use of PPV for the prevention of invasive pneumococcal disease (IPD) in adults. A structured review of the impact of model assumptions on cost-effectiveness ratios was undertaken. Cost per life year gained (LYG) or quality adjusted life year (QALY) were reported in 2007 US dollars. RESULTS The literature search identified 31 studies, 19 of which reported some cost data but did not include cost–effectiveness data for PPV-23 vaccination. All but one of the remaining twelve studies compared PPV-23 vaccination with no vaccination, and these were included in this analysis. Vaccination of over 65 year olds with PPV-23 for the prevention of IPD was found to be cost-effective with incremental cost effectiveness ratios ranging from 2007 $9,810 to $26,160 per LYG and from $9.08 (cost-saving) to $53,955 per QALY. Review of model parameters revealed that the results of these studies have to be considered in the light of limitations of available data on vaccine effectiveness, disease incidence, and case-fatality ratios. CONCLUSIONS All the reviewed studies reported that PPV-23 is a cost-effective, and in some cases a cost-saving, vaccination strategy for the prevention of IPD in the elderly. Further economic evaluation of PPV-23 may be warranted based on the availability of new data on vaccine efficacy, IPD incidence and case fatality in the adult population in the post-PCV-7 era.