Pneumococcal disease is a leading cause of morbidity and mortality in children globally. Pneumococcal conjugate vaccines (PCVs), available since early 2000, had proven efficacy to prevent invasive pneumococcal disease (IPD)-the sever form of pneumococcal infections. For Australian children PCV had been publicly funded through the national immunisation program, initially in 2001 for those with increased disease risk which included Aboriginal and Torres Strait Islander children and from 2005 for all children. The schedule of PCV used in Australia comprising three doses at age 2, 4 and 6 months (called 3+0 schedule) was unique for a developed country. The first PCV used was one covering 7 serotypes of pneumococcus (7vPCV) and in 2011 a PCV that covered 6 more serotypes (13vPCV) replaced 7vPCV. Research contained in this thesis is the first to assess how well PCV prevented IPD among Australian children. After 9 years of combined PCV use IPD in young children declined by over 80%. Together with the added benefit of herd immunity that led to large reductions in IPD in older age groups there was a halving of the all-age total IPD burden. Vaccine effectiveness (VE) of 3 doses against vaccine-type IPD in infancy was ~90% for both PCVs. A major finding in this research was the 5 times higher odds of vaccine-type IPD if the last PCV dose was 24–36 months ago compared to within the last 12 months. This finding of waning VE was a vital piece of evidence that supported the recommendation to move the 3rd dose of 13vPCV in the 3+0 schedule to become a booster dose (i.e. 2+1 schedule) for Australian children from July 2018. Using a data linkage method the impact of PCVs on IPD in children with underlying medical conditions predisposing to pneumococcal infection was explored separately. This highlighted the persistent IPD burden in children with immunosuppression, splenic dysfunction and breach in the CSF barrier, possibly due to opportunistic infection from non-vaccine serotypes.