OBJECTIVES: To assess the cost-effectiveness of mass vaccination for varicella, based on a dynamic model of varicella and zoster. METHODS: Priorix-TetraTM (GlaxoSmithKline Biologicals’ measles, mumps, rubella, and varicella: MMRV) vaccination is highly protective against measles, mumps, rubella and varicella and can result in fewer zoster cases in the long term. Replacing PriorixTM (GlaxoSmithKline Biologicals’ measles, mumps, rubella; MMR) with Priorix-TetraTM can sustain a high vaccine coverage rate for varicella, which might be harder to achieve with monovalent varicella vaccination. The outcome of varicella mass vaccination was predicted using a dynamic transmission model. French costs and event rates per varicella and zoster case (hospitalisation, GP visits, complications and deaths) were applied. Probabilistic sensitivity analysis was performed. RESULTS: Mass vaccination decreased varicella incidence from 12,571 to 4,859 per million person-years. After a slight initial increase, zoster incidence decreased as the vaccinated cohort aged. The large reduction in varicella and zoster cases with Priorix TetraTM resulted in a significant number of complications avoided and more QALYs saved, versus MMR. The direct costs of vaccination in year 1 were €302,840 with MMRV versus €207,906 with MMR, due to the higher cost of the tetravalent vaccine. Significant indirect cost savings were achieved compared with MMR; from €52,043 in year 1 to €1.7 million every year in the post-vaccination steady-state situation (reached after around 30 years). The cumulative direct cost/QALY saved was €83,000 (year 1, coverage ≈20% of MMR replaced), €18,100 (year 5, coverage ≈ 100% of MMR) and €14,150 (year 30). MMRV was the dominant cost-effective strategy compared with MMR when indirect costs were included. CONCLUSIONS: Vaccination with MMRV provided more QALYs, resulted in fewer complications and deaths, and reduced direct and indirect costs (excluding vaccine costs) when compared with vaccination with MMR. The cost/QALY was €83,000 in year one, dropping to below €20,000/QALY thereafter.