Background: Surveillance of trends in antibiotic resistance and serotypes of Streptococcus pneumoniae strains in France relies on a network comprising the regional pneumococcal surveillance centers, the National Pneumococcal Reference Center, and the French Institute for Public Health Surveillance. Methods: Between 2009 and 2013, the 23 regional pneumococcal surveillance centers (ORPs) collected and analyzed 13,033 pneumococcal strains, including 2,953 isolated from children and 10,080 from adults. Results: During this period, the number of isolated strains decreased significantly, by 42.1%. The decrease was particularly marked among children, both for invasive infections (59.7%) and for pus from acute otitis media (74.4%). Among adults, the number of strains isolated from invasive infections decreased by 31.0%. Concurrently, there was a decrease in strains with reduced susceptibility to penicillin G (34.2% in 2009 vs. 25.7% in 2013), as well as a decrease in resistance to amoxicillin (17.9% in 2009 vs. 11.6% in 2013) and to cefotaxime (9.7% in 2009 vs. 6.0% in 2013). Finally, in 2009, the prevalence of strains belonging to the serotypes included in the PCV13 pneumococcal vaccine was 64.2%, and in 2013, it was 35.6%. At the same time, serotypes 12F, 22F, 24F, 15A, 10A, and 23B, which are not included in the PCV13 vaccine, were on the rise. Conclusion: surveillance of resistance and serotypes remains essential because S. pneumoniae infections represent a major public health challenge due to their frequency and severity.