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Summary: Objectives: To evaluate the susceptibility patterns among Streptococcus pneumoniae recovered during the years 2010–2012 and to correlate these with serotypes. Methods: Pneumococci from invasive sites were serotyped by sequential multiplex PCR and/or Quellung reaction. Etest strips were used to determine the minimal inhibitory concentrations, and the Clinical and Laboratory Standards Institute (CLSI) guidelines were used for interpretation. Genetic determinants of macrolide resistance were assessed by PCR, and the occurrence of the D phenotype was analyzed following the recommendations of the CLSI. Results: One hundred fifty-nine S. pneumoniae were studied; most were recovered from blood and were associated with serotypes 14, 3, 4, 23F, 20, 7F, 12F, 19A, and 19F. Pneumococcal conjugate vaccine PCV7, PCV10, and PCV13 and 23-valent polysaccharide vaccine serotypes represented 38.2%, 48.7%, 64.5%, and 85.5%, respectively. β-Lactam non-susceptibility (non-meningitis) was basically related to serotype 19A. For meningitis, it was observed in 21.4% (serotypes 14, 3, 9V, 23F, and 24F). Resistance to erythromycin occurred in 8.2% and mefA was the most common macrolide genetic determinant. One isolate was resistant to levofloxacin. Non-susceptibility to trimethoprim–sulfamethoxazole was 37.7% and to tetracycline was 22.0%. Conclusions: Our population of pneumococci represents a transition era, soon after the introduction of PCV10. Non-susceptible patterns were found to be associated with classical PCV serotypes (especially serotype 14), which is still highly prevalent, and non-PCV10 ones (19A), which may disseminate, occupying the biological niche left by the vaccine serotypes. [Copyright &y& Elsevier]