Meningococcal C conjugate vaccine was introduced into clinical practice in the UK before phase 3 trials had been undertaken. We therefore did a case-control study in teenagers to assess vaccine effectiveness. All cases (n=31) enrolled had laboratory confirmed meningococcal C disease. We also enrolled between one and three controls (n=65) per case, matched by age, sex, and general practitioner. Three patients and 23 controls had been vaccinated. The protective effectiveness of the vaccine, estimated by conditional logistic regression, was 93% (95% CI 39-99), which is similar to screening method estimates. The estimated protective effectiveness varied little when potential confounding risk factors were taken into account. Our findings indicate that the vaccine is highly protective against invasive meningococcal C disease.