BACKGROUND: Several studies have shown that pneumococcal vaccination of older persons would be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection for this condition is uncertain. Given much better evidence of vaccination effectiveness against invasive disease, studies showing that vaccination is cost-effective in preventing invasive disease alone could provide strong support for public policies to vaccinate older persons. METHODS: We examined the cost-effectiveness of preventing invasive pneumococcal infection by vaccination with the 23-valent pneumococcal polysaccharide vaccine of persons > or = 65 years in age in Belgium. The direct medical costs expressed per quality adjusted life year (QALYs) of a cohort of vaccinated persons was compared with the costs per QALY in a cohort of persons who are not vaccinated. RESULTS: Preventing invasive pneumococcal infections by vaccinating elderly persons clearly benefits people's health. By vaccinating 10,000 persons over 65 years of age, approximately eight QALYs can be gained compared with no vaccination. Achieving these health benefits however requires additional costs,: 30,000 ECU per QALY gained. The cost-effectiveness ratio is slightly better (i.e. 25,000 ECU per QALY) for the age group 65-75 years, and slightly worse (i.e. 35,000 ECU per QALY) for the age group 75-84 years. It increases sharply to 77,000 ECU per QALY for the persons over 85 years of age. An extensive one-dimensional sensitivity analysis did not greatly affect these results. If vaccination is also clinically effective in preventing pneumococcal pneumonia, vaccinating all elderly persons is cost saving. CONCLUSION: Using empirical epidemiological data, pneumococcal vaccination to prevent invasive pneumococcal disease is acceptably to moderately cost-effective in Belgium. On the basis of our findings, we believe public health authorities should consider policies for encouraging pneumococcal vaccination for all persons > or = 65 years in age.