In the Health Care Area of Santiago de Compostela, during three years (2004-2006), we studied 218 Streptococcus pneumoniae isolates from invasive disease (10 CSF, 133 blood culture, 7 pleural fluid, 9 corneal ulcer and 59 lower respiratory tract), to determine the predominant serotypes and antimicrobial susceptibility. 77.1% of the isolates were from adults and 22.9% from pediatric patients. There were 33 different serotypes, six of them occurring in more than 5% of cases, in decreasing order: 19 (16.97%), 3 (11.46%), 1 (10.55%), 14 (10.55%), 23 (6.88%) and 6 (6.88%). The predominant serogroup in CSF was 19 and in blood culture predominant serogroups were 19, 1, 14 and 3. 63.76% of the isolates were susceptible to all antibiotics tested. The most frequent resistance phenotypes were to erythromycin (24.31%), followed by penicillin (18.34%). Both phenotypes were associated with serotypes 19, 14 and 6. The resistance to levofloxacin was 0.9% and 0.5% to cefotaxime. We did not find any vancomycin resistance.