The incidence of invasive meningitis disease (IMD) is increasing in Australia. A conjugate vaccine of meningococcal polysaccharide serogroups A, C, W and Y (MenACWY) is currently indicated for infants aged 12 months on the Australian National Immunisation Program. This study sought to determine the cost-effectiveness of a broader MenACWY vaccination program for Australians aged 15 to 19 years. A Markov model was constructed to simulate the incidence and consequences of IMD in Australians aged 0–84 years, with follow up until age 85 years. The model comprised four health states: ‘Alive with no previous IMD’, ‘Alive, post IMD without long-term complications’, ‘Alive, post IMD with long-term complications’ and ‘Dead’. Decision analysis compared the clinical consequences and costs of a vaccination program versus no vaccination from the perspective of the Australian health care system. Age-specific incidence of IMD and fatality rates were derived from Australian surveillance data. Vaccine coverage, vaccine efficacy and herd immunity were based on published data. The total cost for MenACWY vaccination was AU$56 per dose. Costs and health outcomes were discounted by 5% per annum (in the base-case analysis). Compared to no vaccination, a MenACWY vaccination program targeted at Australians aged 15–19 years was expected to prevent 1664 IMD cases in the Australian population aged 0–84 years followed up until age 85 years. The program would lead to 1131 life years (LYs) and 2058 quality adjusted life years (QALYs) gained at a total cost of AU$115 million (all discounted values). These equated to incremental cost-effectiveness ratios of AU$101,649 per LY gained and AU$55,857 per QALY gained. A probabilistic sensitivity analysis demonstrated a likelihood of cost-effectiveness of 34.6%, assuming a willingness to pay threshold of AU$50,000 per QALY gained. The likelihood of this program being cost-effective under a willingness to pay threshold AU$50,000 per QALY gained is 35%.