This study compares the cost-effectiveness of a control strategy for serogroup C meningococcal disease (CMD) relying on surveillance and implementation of a mass immunization campaign effective 1 year after the beginning of an epidemic with strategies based on routine immunization, using either three doses of serogroup C conjugate vaccine given in early infancy or one dose at 1 year of age. The simulation model is based on 25 birth cohorts followed up to age 24 years, and seven epidemiological scenarios including low and high level endemicity, and one to five epidemics over a 49-year period. Epidemiological and cost data were mainly collected in the province of Quebec, Canada. Results indicate that the most effective strategy is a three-dose routine program, with the least effective strategy being mass immunization. A one-dose routine program is the most cost-effective strategy in most likely scenarios. In a societal perspective with a vaccine purchase price of CDN$ 50 per dose, the average incremental cost of the one-dose strategy would be $ 190,000 per case averted, US$ 23,000 per life-year gained, and US$ 42,000 per QALY gained. If vaccine-induced immunity is waning rapidly, mass immunization or routine vaccination with booster dose(s) would be the best control options.