Abstract: Considering high disease burden of pneumococcal disease globally, World Health Organization (WHO) recommends pneumococcal conjugate vaccine (PCV) should be included into national immunization program in all countries. However, the difficulty in evaluating vaccine effectiveness for pneumococcal diseases slows down the new vaccine development due to low incidence of the disease and hard to diagnosis and surveillance. A surrogate indicator for vaccine efficacy will improve the vaccine research and development effectively. The serological efficacy data and vaccine effectiveness data from clinical trials for 7-valent pneumococcal conjugate vaccine (PCV7) was used by WHO to establish an antibody protective threshold against invasive pneumococcal diseases (IPD). WHO suggests that a 0.35 μg/ml immunoglobulin G (IgG) level tested by enzyme-linked immunosorbent assay (ELISA) could be considered as a protective level for PCV preventing IPD, and using this threshold to estimate the vaccine effectiveness against IPD when evaluating a new PCV for its licensure. However, this surrogate indicator should not be used for evaluating vaccine effectiveness for non-invasive pneumococcal diseases. Also, the threshold should be considered at population level and it does not indicate to prevent every IPD at individual level.