Streptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23 serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50 years. 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 €300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about €83 000, €60 000 and €52 000 per QALY gained in 50–64, 65–74 and 75–84 year olds, whereas for PCV13 this is about €171 000, €201 000 and €338 000, 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 75 years 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.