OBJECTIVES: To estimate the health outcomes of vaccination with the new 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PH¡D-CV) compared with no vaccination. METHODS: A cross-sectional population-based model was used to estimate the impact of vaccination over 1-year at vaccine steady-state and to perform an incremental cost-effectiveness analysis, comparing 3+1 dose vaccination schedule of PH¡D-CV vs no vaccination. Universal massive vaccination (UMV) for pneumococcal disease is currently not compulsory according to the National Vaccination Calendar in Spain. The analysis was performed from the National Health System perspective. Input data were obtained from the Ministry of Health public database and published regional studies, and was completed by expert opinion to validate model assumptions on the vaccination effects of herd-protection for invasive disease, serotype replacement, serotype cross-protection and resource use. The main clinical outcomes measured were invasive pneumococcal disease (meningitis and bacteraemia/sepsis), acute otitis media (AOM), myringotomies and hospitalised pneumonia. These were measured by reduction in the disease cases and their associated costs. RESULTS: Preliminary results indicate that PHiD-CV could prevent annually and for all ages 4.352 hospitalisations (272 meningitis, 2.013 bacteraemia/sepsis and 2.067 pneumonias), 2.964 myringotomies and 180.361 ambulatory GP-visits for AOM, overall reducing disease costs in €34.2M, mainly due to less AOM costs (€15.1M). Implementation of PHiD-CV could be a cost-effective intervention compared with no vaccination expressed as cost per QALY gained of €18,597. CONCLUSIONS: The analysis predicts that vaccination with PHiD-CV could produce a significant health improvement and substantial disease cost offset from the National Health System perspective when compared to no vaccination. Results support that the implementation of PHiD-CV UMV should be considered by Public Health decision-makers.