OBJECTIVES: A 7-valent pneumococcal conjugate vaccine (PCV7, Prevenar*) is currently recommended for childhood vaccination in the UK. A 10-valent vaccine (PCV10, Synflorix, GSK) is licensed and a 13-valent vaccine (PCV13, Wyeth) is currently being reviewed by regulatory authorities. This study estimated the cost effectiveness of PCV13 and PCV10 compared to PCV7 for childhood vaccination in the UK. METHODS: A steady state, static cohort model was constructed comparing the incremental benefit of PCV13 compared to PCV7 and PCV10 compared to PCV7 for vaccination of the entire birth cohort. In children, the model considered the incidence and subsequent costs of four disease states: pneumococcal meningitis; pneumococcal bacteraemia; all cause pneumonia and acute otitis media (AOM). In adults the model considered invasive pneumococcal disease (IPD) and all cause pneumonia, exploring the potential impact of herd immunity. Sensitivity analyses were conducted on incidence, mortality rates, vaccine efficacy, serotype coverage and costs, discount rate, uptake and non-vaccine serotype prevalence. RESULTS: The model estimated that, in addition to PCV7, PCV13 (PCV10) would annually reduce the incidence of IPD by 888 (573) cases, prevent 23 (16) deaths, increase the number of life years gained by 509 (343), increase QALYs gained by 611 (375) and reduce medical costs by £5.2m (£3.3m). The benefits of the new vaccines are sensitive to efficacy and the magnitude and pattern of herd immunity that emerges. CONCLUSIONS: Our analysis found that PCV13 vaccination in the UK will be more effective than PCV10 in reducing the burden of pneumococcal disease when compared to PCV7 and will further reduce cost. Final cost-effectiveness will depend on the emergence of herd immunity benefits in the UK, the impact on AOM and pneumonia, the vaccination schedule deployed and price of PCV13 and PCV10.