OBJECTIVES: In Germany, vaccination of infants with a 13-valent pneumococcal conjugate vaccine (PCV13) and of individuals >=60 years with a 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended to prevent pneumococcal diseases. Recently, PCV13 was also approved for individuals >=50 years. The study assesses the cost-effectiveness of four vaccination strategies targeting adults >=60 years in Germany: no vaccination, vaccination with PCV13 only, vaccination with PPSV23 only, and sequential-vaccination (PCV13+PPSV23). METHODS: A susceptible-infected-susceptible type model based on ordinary differential equations was developed to capture the dynamic transmission of pneumococcal carriage. The model compartments were further stratified by age- and pneumococcal serotype-groups. Model parameters were either retrieved from the literature or obtained by fitting against local incidence data. The epidemiological impact of childhood PCV13-vaccination (herd and serotype replacement effects) on incidence and serotype mix among adults as well as components of the four adult vaccination strategies was implemented in the model. A health-economic model was built to compute the incremental cost-effectiveness ratios (ICER) per QALY using German cost data. The robustness of the model results was assessed through sensitivity analyses regarding uncertain input data. RESULTS: In the base case, the ICER of PPSV23 vs. no vaccination was €24,085/QALY. Immunization with PCV13 alone was dominated by PPSV23-vaccination. Sequential vaccination vs. PPSV23 vaccination resulted in €400,528/QALY. Main reason for the higher ICERs of the latter two strategies was a sharp decline in PCV13-serotypes prevalence among adults as an indirect result of infant PCV13-vaccination. Sensitivity analyses identified the effectiveness of PPSV23 against non-invasive pneumococcal pneumonia to have a substantial impact on the model results and be a major source of uncertainty due to the heterogeneity in reported effectiveness/efficacy data. CONCLUSIONS: From a health economic perspective, PPSV23 would be the preferred vaccine to be used for the prevention of pneumococcal disease in adults in Germany.