This study evaluated the impact of heptavalent pneumococcal conjugate vaccine (HPCV) on invasive pneumococcal disease (IPD) in children aged < or = 5 years in Barcelona, Spain. The incidence of IPD, vaccine uptake and prevalence of nasopharyngeal colonisation were analysed in two different periods: 1999-2001 (pre-licence period), and 2002-2004 (post-licence period). In total, 121 cases of IPD were identified. The overall incidence of IPD decreased from 96.9 cases/100,000 to 90.6 cases/100,000 (OR 0.93, 95% CI 0.69-1.26, p 0.71) between the two periods. The proportion of cases caused by non-vaccine-related serotypes (NVS) increased from 21% to 43.7% (OR 2.9, 95% CI 1.2-7, p 0.01). IPD was diagnosed in seven vaccinated children, six of whom were infected by NVS. There was a trend of diminishing prevalence of resistance to penicillin and macrolides in 2002-2004. The incidence of empyema increased from 1.7 to 8.5/100,000 (OR 4.5, 95% CI 0.91-18, p 0.06). The rate of vaccination ranged from 4.8% to 34%. It was concluded that the rates of IPD in this area did not decrease following the introduction of HPCV. The low uptake of vaccine and the greater proportion of colonisation/infection by NVS probably explain these findings. A trend of increasing empyema was also apparent. A decrease in the prevalence of penicillin and macrolide resistance paralleled the progressive uptake of vaccine.