In the last two decades, an increasing trend in the incidence of pneumococcal disease in Europe has been reported. We investigated the effect of the use of the heptavalent pneumococcal conjugate vaccine (PCV7) in an area of northern Spain, where all recorded cases of invasive pneumococcal diseases (IPD) were included (n = 450; 91 between 1996–2007 in children aged <5 years and 359 between 1998–2007 in adults aged >64 years). All isolates were serotyped. In children, the overall IPD incidence did not significantly decrease after the introduction, in late 2001, of PCV7. However, the incidence of PCV7 serotypes significantly decreased by 137.2% from 31.59 cases/100,000 population in 1996–2001 to 13.42 in 2002–2007 (95% confidence interval [CI] −27.2 to −342.4%), as did the overall rates of penicillin resistance (from 45.6 to 18.6%) and multiresistance (from 30.3 to 11%). In older adults, the overall IPD incidence showed a non-significant increase due to non-PCV7 serotypes, which seemed to continue a previous trend in our region.