Abstract Background In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for children aged 14 months was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting individuals aged 14–18 years was executed. We investigated the impact of MenACWY vaccination implementation in 2018–2020 on incidence rates and estimated vaccine effectiveness (VE). Methods We extracted IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group–specific incidence rate ratios by comparing incidence rates before (July 2017–March 2018) and after (July 2019–March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method. Results Overall, the IMD-W incidence rate declined by 61% (95% confidence interval [CI], 40 to 74). It declined by 82% (95% CI, 18 to 96) in the vaccine-eligible age group (individuals aged 15–36 months and 14–18 years) and by 57% (95% CI, 34 to 72) in vaccine-noneligible age groups. VE was 92% (95% CI, –20 to 99.5) in vaccine-eligible toddlers (aged 15–36 months). No IMD-W cases were reported in vaccine-eligible teenagers after the campaign. Conclusions The MenACWY vaccination program was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine-noneligible age groups may be caused by indirect effects of the vaccination program. However, disentangling natural fluctuation from vaccine effect was not possible. Our findings encourage the use of toddler and teenager MenACWY vaccination in national immunization programs.