Summary Objectives Streptococcus pneumoniae is frequently isolated from carrier children, but it also causes localized and invasive diseases. Increasing incidence of chemoresistance can affect the efficacy of empiric therapy and it motivates interest in primary prophylaxis. The study aims to investigate clinical and microbiological features of paediatric pneumococcal infections in an Italian province. Methods Retrospective clinical analysis of 640 children, hospitalized from 1992 to 2006 with one culture positive for S. pneumoniae, was performed. Chemosusceptibility tests and serotyping were carried out on isolates; statistical analysis was applied to compare variables. Results Overall, 47.8% were carriers, 49% and 3.2% had, respectively, a localized or invasive disease; S. pneumoniae aetiology accounted for 25% of meningitis and 16% of sepsis. On the total isolates, 10.2% were penicillin non-susceptible, 35.15% were erythromycin resistant, with increasing rates over years. Prevalent invasive serotypes were 1 (38.1%) and 7F (9.5%). Conclusions The study sustains pneumococcal disease relevance in children, on the strength of a 15 year observation. Long time period can represent a limit due to population characteristics changing; a selection bias could also be present due to hospitalized only patient analysis. However, we documented variable evolution of chemoresistance and a peculiar serotype spreading, offering microbiological basis for an appropriate clinical approach.