OBJECTIVES: To evaluate cost–effectiveness of pneumococcal vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D vaccine (PHiD-CV) compared with 13-valent pneumococcal conjugate vaccine (PCV-13) and no vaccination in The Kingdom of Saudi Arabia (KSA). METHODS: A steady state model with a one-year time horizon was developed to project the impact of vaccination on the incidence of pneumococcal and non-typeable Haemophilus Influenzae (NTHi) infections in children aged 0-10 years. Data sources: Pneumococcal serotype distribution is based on 176 invasive S. pneumoniae isolates collected in KSA hospitals in 2005 to 2008. IPD, hospitalised pneumonia and acute otitis media (AOM) disease incidence rates were based on a study from 12 hospitals in KSA, data from Turkey and benchmarks with other countries. Vaccines coverage rates for IPD of 79.3 % and 83.9% for PHiD-CV and PCV-13, payer perspective, no herd protection and a (3+1) vaccination schedule was assumed. RESULTS: PHiD-CV and PCV-13 are projected to prevent more cases of invasive disease (724; 749 respectively) and equal number of pneumonia hospitalizations (510; 510 respectively) compared to no vaccination. PHiD-CV and PCV-13 are projected to prevent additional myringotomies (4783; 2365 respectively) and GP visits due to AOM (170,936; 84,518 respectively) compared to no vaccination strategy. Vaccinating a birth cohort with PHiD-CV or PCV-13 is expected to generate 8,966; 8,888 more QALYs compared to no vaccination. At vaccine steady state cost-savings related to disease burden reduction are $14.1M and $7.6M for PHiD-CV and PCV-13 respectively compared with no vaccination. Sensitivity analyses indicate that incidence rate of IPD has the biggest impact on results. CONCLUSIONS: Incremental cost-effectiveness ratios indicate that both vaccines are cost effective interventions. PHiD-CV dominates PCV-13 because it has a larger potential QALY gain and larger cost offset.