Abstract: New Zealand has experienced a prolonged epidemic of meningococcal B disease since 1991. The epidemic has waned significantly since its most recent peak in 2001. A strain-specific vaccine, MeNZB, was introduced to control the epidemic in 2004, achieving 81% coverage of people under the age of 20. The vaccine was rolled out in a staged manner allowing the comparison of disease rates in vaccinated and unvaccinated individuals in each year. Vaccine effectiveness in people aged under 20 years is estimated using a Poisson regression model in the years 2001–2008, including adjustments for year, season, age, ethnicity, region and socioeconomic status. Further analyses investigate the dose response relationship, waning of the vaccine effect after one year, and cross-protection against other strains of meningococcal disease. The primary analysis estimates MeNZB vaccine effectiveness to be 77% (95% CI 62–85) after 3 doses and a mean follow-up time of 3.2 years. There is evidence for a protective effect after 2 doses 47% (95% CI 16–67), and no evidence for a waning of effectiveness after one year. Simultaneous modelling of invasive pneumococcal disease and epidemic strain meningococcal B suggests a degree of residual confounding that reduces the effectiveness estimate to 68%. There is evidence for some cross-protection of MeNZB against non-epidemic strains. The MeNZB vaccine was effective against the New Zealand epidemic strain of meningococcal B disease. Between July 2004 and December 2008 an estimated 210 epidemic strain cases (95% CI 100–380), six deaths and 15–30 cases of severe sequelae were avoided in New Zealand due to the introduction of the MeNZB vaccine. [Copyright &y& Elsevier]