Introduction Streptococcus pneumoniae (the pneumococcus) is a leading cause of death in under-five children. The HIV/AIDS epidemic in sub-Saharan Africa contributes substantially to the pneumonia burden in the region. Vaccination against pneumococcus is a core component of the pneumococcal disease control program. It is a good, practical and cost-effective option to overcome some of the difficulties in facing the factors which facilitate the occurrence of pneumococcal disease. The aim of this study was to assess the persistence of efficacy of 9-valent pneumococcal conjugate vaccine (PCV9) against radiographically-confirmed pneumonia among children over 24 months of age in comparison to children before 6 months and between 6 and 24 months of age in South Africa. Materials and methods The study was an analytic cohort study using secondary data of a randomised controlled trial (RCT) of PCV9 from the Respiratory and Meningeal Pathogens Research Unit (RMPRU), University of the Witwatersrand. STATA and Epi-info computer software programs were used in the analysis. Findings Three thousand seven hundred PCV9 trial participants, who had chest x-ray records, form the cohort of the study. Overall PCV9 efficacy against radiographically-confirmed pneumonia was 7%. PCV9 was more efficacious against radiographically-confirmed pneumonia in 6 to 24 month of age children (21%) compared to under-6 month (0%) and beyond-24 month of age children (-5%). Partial PCV9 vaccination was more efficacious against radiographically-confirmed pneumonia than full vaccination. The association between partial and complete vaccination and radiographically-confirmed pneumonia was not statistically significant, however. HIV infection profoundly affected the efficacy of PCV9 in all age groups. Other factors which were associated with radiographically-confirmed pneumonia were clinical pneumonia, more than two previous pneumonia admissions and presence of pneumonia predisposing factors. Conclusion and recommendations PCV9 vaccination had limited efficacy against radiographically-confirmed pneumonia. However, it was more effective against radiographically-confirmed pneumonia in 6 to 24 month old children. Partial vaccination was more efficacious than a full course (given at 6, 10 and 14 weeks of age). Adoption of two primary doses of PCV9 with one booster dose, in-depth studies to investigate the factors that affect PCV9 efficacy, raising awareness about the potential effect of these factors on radiographically-confirmed pneumonia and the improvement of HIV/AIDS interventions are recommended.