OBJECTIVES: We evaluated the effect of the infant 7-valent pneumococcal conjugate vaccine (PCV7) program on the serotype distribution in invasive pneumococcal disease in the Belgian population. METHODS: Serotyping was performed on 13,998 bacteraemic and pleural fluid isolates sent to the National Reference Laboratory between 2002 and 2010. We compared the distribution of serogroups (SGs) between the pre- (2002-2004) and post-PCV7 (2007-2010) era for children (<18 years), adults (18-59 years) and older individuals (≥60 years). RESULTS: The proportion of cases caused by PCV7-SGs in subjects <18 years decreased from 69% pre-PCV7 to 26% post-PCV7 (p<0.005) and the majority of cases caused by PCV7-SGs were caused by SG 19. Post-PCV7, the prevalence of PCV7-SGs decreased from 38% to 29% and from 57% to 35% in subjects in the age groups 18-59 and ≥60 years, respectively (p<0.005). Post-PCV7 the prevalence of SGs 1, 7 and 19 increased significantly in subjects aged <18 years. The increase of SG19 was caused by an increase of serotype 19A in this age group (p<0.005). After the introduction of infant PCV7 the largest rise in prevalence occurred for SGs 7, 12 and 22 (p<0.005) in the two older age categories. Post PCV7, the overall PCV13 and 23-valent pneumococcal polysaccharide vaccine coverage rates decreased from 85% to 69% and from 96% to 93%, respectively (p<0.005). CONCLUSIONS: PCV7 has an impact on SG distribution of invasive pneumococcal disease isolates of vaccinated and unvaccinated subjects. SG replacement forms a major threat to the success of PCV7. PCV13, including several additional replacement serotypes (STs 1, 7F, 19A), represents an attractive alternative.