Background: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. Methods: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. Results: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6–1.0) among IPP cases compared to matched controls. Conclusion: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.