Abstract: Streptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50years. We developed and parameterized a static multi-cohort model to estimate the incremental cost-effectiveness and budget-impact of these vaccines at different uptake levels. Using three different vaccine efficacy scenarios regarding non-invasive pneumococcal pneumonia and extensive uni- and multivariate sensitivity analyses, we found a strong preference for PPV23 over PCV13 in all age groups at willingness to pay levels below Euro300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about Euro83000, Euro60000 and Euro52000 per QALY gained in 50-64, 65-74 and 75-84year olds, whereas for PCV13 this is about Euro171000, Euro201000 and Euro338000, respectively. Strategies combining PPV23 and PCV13 vaccines were most effective but generally less cost-effective. When assuming a combination of increased duration of PCV13 protection, increased disease burden preventable by PCV13 and a 75% reduction of the PCV13 price, PCV13 could become more attractive in <75 year olds, but would remain less attractive than PPV23 from age 75years onwards. These observations are independent of the assumption that PPV23 has 0% efficacy against non-invasive pneumococcal pneumonia. Pneumococcal vaccination would be most cost-effective in Belgium, when achieving high uptake with PPV23 in 75-84 year olds, as well as by negotiating a lower market-conform PPV23 price to improve uptake and cost-effectiveness.