Objectives To update cost effectiveness estimates for the four dose (3+1) schedule of the seven valent pneumococcal conjugated vaccine (PCV-7) in the Netherlands and to explore the impact on cost effectiveness of reduced dose schedules and implementation of 10 valent and 13 valent pneumococcal vaccines (PCV-10 and PCV-13). Design Economic evaluation comparing PCV-7, PCV-10, and PCV-13 with no vaccination using a decision tree analytic model built from data in previous studies. Setting The Netherlands. Population A cohort of 180 000 newborns followed until 5 years of age. Main outcome measures Costs; gains in life years and quality adjusted life years (QALYs); and incremental cost effectiveness ratios. Results Under base case assumptions—that is, assuming a five year protective period of the vaccine and no assumed net indirect effects (herd protection minus serotype replacement) among children aged over 5 years—vaccination with PVC-7 in a four dose (3+1) schedule was estimated to prevent 71 and 5778 cases of invasive and non-invasive pneumococcal disease, respectively, in children aged up to 5 years. This corresponds with a total net gain of 173 life years or 277 QALYs. The incremental cost effectiveness ratio of PCV-7 was estimated at €113 891 (£98 300; $145 000) per QALY, well over the ratio of €50 000 per QALY required for PCV-7 to be regarded as potentially cost effective. A three dose (2+1) schedule of PCV-7 reduced the incremental cost effectiveness ratio to €82 975 per QALY. For various assumptions and including 10% of the maximum net indirect effects among individuals aged 5 years and over, PCV-10 and PCV-13 had incremental cost effectiveness ratios ranging from €31 250 to €52 947 per QALY. Conclusions The current Dutch infant vaccination programme of four doses of PCV-7 is not cost effective because of increases in invasive disease caused by non-vaccine serotypes, which reduces the overall direct effects of vaccination and offsets potential positive herd protection benefits in unvaccinated individuals. ...