OBJECTIVES: To determine the cost-effectiveness of pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) when compared with 7-valent pneumococcal conjugate vaccine (PCV-7) and with no vaccination for the prophylaxis of invasive (ID) and non-invasive pneumococcal diseases in Poland. METHODS: A Markov cohort model was used with a starting birth cohort of 393 506 infants. The Streptococcus pneumoniae serotype distribution from Czech Republic setting was selected as a proxy for Polish data. The effectiveness and safety data came from a meta-analysis of clinical trial results. Limited cross-protection of serotypes 6A and 19A, herd protection and serotype replacement were included into the model design. Ten years time horizon (the period of direct vaccine effect) and 96% vaccine coverage rate were considered. Direct medical costs were collected during January-March, 2009 from a public payer’s and patient’s perspective. Price parity between vaccines was assumed. Sensitivity analysis was carried out. Annual discount rate for cost and effect was 5.0% and 3.5% respectively. RESULTS: Base-case analysis of PHiD-CV shows that mass vaccination of the birth cohort reduced the number of ID by 120, pneumonia by 17,102, and acute otitis media events by 113,768 cases over 10 years. When compared with PCV-7 and no vaccination, PHiD-CV offered a Quality Adjusted Life Year gain (QALY) of 0.0045 and 0.0068 per vaccinated child respectively. Prophylaxis with PHiD-CV instead of PCV-7 induced cost savings of 39.97 PLN per child. Vaccination with PHiD-CV dominated PCV-7 but when compared with no vaccination an incremental cost per QALY was estimated at 54,549 PLN. Sensitivity analysis showed consistency in the results. A few analysis limitations were identified such as length of vaccine protection and reliable serotype distribution data. CONCLUSIONS: Compared with no vaccination the model indicates that PHiD-CV is cost-effective in Poland and has superior economic profile to PCV-7.