OBJECTIVES: Different model types can be used for assessing the economic value of new interventions but they may give different results. Our study-objective is to compare the economic results for pneumococcal vaccination between a cross-sectional population model and a cohort model. If the indirect vaccine effect is large, the demographic composition of the population may heavily influence the results. METHODS: Both cohort and population models were developed in Excel, and adapted to the UK to evaluate the cost-effectiveness of PHiD-CV (pneumococcal Haemophilus influenzae-protein D conjugate vaccine), 3+1 dosing schedule, 100% coverage, vs. no vaccine. The models estimate the vaccine effect on meningitis, bacteremia, pneumonia and otitis media. For the population model the evaluation occurs at vaccine steady-state condition over a one-year period across the whole UK population, whilst for the cohort model one birth cohort is followed over lifetime. Input data from literature, national databases and trial results were used; natural mortality was only included in the cohort model; the population model used the current demographic distribution. Costs were assessed from the UK healthcare perspective. Incremental cost-effectiveness ratios (ICERs) were derived from both models and compared. Sensitivity analysis was performed on demographic changes in the population model. RESULTS: With herd protection and replacement the ICER results for the UK were GBP6,117 per QALY gained in the cohort model and slightly higher in the population model, GBP6,360. Decreasing the number of people in the younger age groups and increasing in the older age-groups by two-fold heavily impacted the population model ICER-results by more than 30%. CONCLUSIONS: Both the population and cohort model provide similar results with the current demographic composition in the UK. However the population model may report more accurate information if the indirect vaccine effect is large, quickly obtained, and the demographic composition of the population is not homogeneous.