Aims: The general aim was to observe the characteristics (serotypes, antimicrobial resistance) of invasive S. pneumoniae strains depending on the time period and patient age and to determine the extent of coverage by currently available vaccines. Specific aims were to determine the serotype distribution and antimicrobial susceptibility of invasive S. pneumoniae and to determine the resistance mechanisms in macrolide and quinolone-resistant isolates. ------ Materials and methods: Invasive pneumococcal strains were collected through the microbiological laboratories engaged in the national antibiotic resistance surveillance organised as the Croatian Committee for Antibacterial Resistance Surveillance. Capsular typing was performed by the capsular swelling method (the Quellung reaction). In vitro susceptibility testing was performed according to the CLSI and the EUCAST guidelines. The presence of macrolide and fluoroquinolone resistance genes was detected by PCR. ----- Results: The overall incidence of invasive pneumococcal disease (IPD) was 2.92 confirmed cases per 100 000 population. Analysis was done in 1666 out of 1854 consecutively collected, non-copy isolates. A total of 32.6% strains were isolated in children <18 years and 30.9% in adults ≥65 years of age. The most prevalent serotypes among children were 14, 6B, 19A, 23F, 18C and 1, while serotypes 3, 14, 19A, 9V, 23F and 7F were the most prevalent among adults. The trend in the serotype distribution was observed only for serotype 1, which was decreasing. Pneumonia was the most common clinical presentation, in the overall population and among adults. Penicillin non-wild type strains (22%) and macrolide-resistant strains (29.4%), mostly belonged to serotypes 14 and 19A. Resistance to fluoroquinolones was detected in 4 isolates only. The coverage by 10-, 13- and 23-valent vaccines was 69%, 74.5% and 90.6%, respectively, for the target population. ------ Conclusions: The incidence of IPD and serotype distribution varied with patient age. All available vaccines have high coverage for the target population and strains with acquired resistance to the antibiotic.