- Background: Recent studies have shown that some Streptococcus pneumoniae serotypes possess a higher potential to cause invasive disease than others. However, it is unknown whether disease potential for specific serotypes is similar for mucosal disease. Our objective was to assess the disease potential of individual S. pneumoniae serotypes causing invasive pneumococcal disease (IPD), acute otitis media (AOM) and acute conjunctivitis (AC) in children. Methods: Serotypes of pneumococcal isolates from children with IPD, AOM and AC were compared with those carried by healthy children aged <3 years. All children resided in the same area and were studied during the same period. Odds ratios for disease were calculated for each diagnosis following multivariate analysis, including gender, age, ethnic group, previous antibiotic treatment and year variability. Results: A total of 5500 isolates were collected: 189 from blood or cerebrospinal fluid, 3200 from middle ear fluid, 348 from conjunctiva and 1763 from nasopharynx of healthy children. A significant positive association with IPD was demonstrated for serotypes 1, 5 and 12F; with AOM for serotypes 1, 3, 5, 12F, 19A and 19F; and with AC for serotype 3 and nontypeable S. pneumoniae. A significant negative association with IPD was demonstrated for nontypeable S. pneumoniae and with AOM for serotypes 6A, 6B, 15A and nontypeable S. pneumoniae. Conclusions: Our results reflect the importance of the polysaccharide capsule in site-specific disease potential and provide useful information regarding disease potential of nonvaccine serotypes shown to be involved in carriage replacement after vaccination with the 7-valent conjugate vaccine.