Australia introduced the 7-valent pneumococcal conjugate vaccine (7vPCV) on the universal infant National Immunisation Program (NIP) in 2005 and replaced it with the 13-valent pneumococcal conjugate vaccine (13vPCV) in 2011, both under a 3 ? 0 schedule. The objective of this analysis was to quantify the clinical and economic impact of the universal infant PCV program in Australia from its introduction. A decision-analytic model was developed to estimate the historical impact of pneumococcal conjugate vaccine (PCV) programs in Australia from a direct health care perspective. Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM) were obtained from available Australian epidemiologic databases supplemented with published data. Costs were from Medicare Benefits Schedule in 2018 Australian dollars and utility weights from published sources. Historical observed changes in disease for the universal PCV NIP era (2005-2017) were compared against a ''no-vaccine'' scenario. The expected incidence for the no-vaccine scenario in years 2005-2017 was calculated using pre-universal PCV NIP era (2001-2004) data. Averted cases, deaths, incremental costs, and quality-adjusted life years (QALYs) were obtained by subtracting the vaccine scenario totals from the no-vaccine scenario totals. From the inclusion in the universal infant NIP, 7vPCV and 13vPCV are estimated to have prevented 1,770,024 cases of pneumococcal disease (IPD = 16,392; OM = 1,575,491; pneumonia = 102,059) and 1195 associated deaths. Over this period, there was a total 24,335 QALYs gained. Costs for the universal infant NIP were offset by $733 million direct costs saved, resulting in an incremental cost-effectiveness ratio of $3347 per QALY gained. PCVs have provided substantial public health and economic value from sustained use in Australia. Results are conservative, since long-term pneumococcal disease consequences and broader socioeconomic benefits were not considered. Maintaining 13vPCV on the Australian infant NIP under the newly implemented 2 ? 1 schedule will likely provide more return on investment and sustained reductions in pneumococcal disease.