This study describes the epidemiological impact of meningococcal C conjugate vaccine on age groups targeted by this vaccination programme in Spain, and estimates high short-term vaccine effectiveness values under field conditions in the 4 years following its introduction. Meningococcal C conjugate vaccine has led to a substantial reduction in incidence of meningococcal serogroup C disease in Spain among age groups targeted for intervention nationwide. Disease surveillance in the 4 years since the vaccine was introduced has enabled vaccine effectiveness (VE) to be estimated. The vaccine registered high short-term VE values but there has been some loss of VE with time. Four years after vaccination, vaccine protection levels exceeded 94% in cohorts immunised during the campaign. Among children vaccinated in routine childhood immunisation programmes, however, long-term VE loss was greater. Accordingly, there is a need for ongoing re-evaluation of VE and ascertainment of long-term vaccine protection. The findings reported would allow to decide on the advisability of revising current vaccination guidelines.