OBJECTIVES: The cost-effectiveness of routine influenza vaccination in people over 65 is accepted. This study compares the incremental cost-effectiveness of the MF59 adjuvanted vaccine Fluad?* to non-adjuvanted vaccines in France in situations where the circulating strain matches the strain prepared in the vaccine, and also where there is antigenic drift – where the circulating strain differs slightly from the one included in the vaccine. METHODS: A decision analysis model was developed using evidence from clinical studies concerning the relative effectiveness of Fluad? and non-adjuvanted vaccines in the over 65 population. Evidence concerning the impact of Fluad? on hospitalisation was taken from an observational study, other resource use parameters and costs from the literature. The analysis was performed from the payer perspective (direct medical costs). RESULTS: Based on the increased protective efficacy of Fluad? compared to non-adjuvanted vaccines, we estimated a reduction in cases of between 11.8% and 23.8% depending on the influenza strain circulating in the community. Using these estimates, for an attack rate of Influenza-like Illness of 5% and a discount rate of 3%, the incremental cost per life year gained (CLYG) ranged from €3,103 to €23,894. In situations where there is antigenic drift (which occurs every 2-5 years), all vaccines are less effective. However, the efficacy of Fluad? falls by only 2%, whereas that of non-adjuvanted vaccines falls by 22%. With antigenic drift, the cost-effectiveness of Fluad? compared to non-adjuvanted vaccines is enhanced due to the better protective effect, and depending on the circulating strain, ranged from being cost saving to an incremental CLYG of €5,709. CONCLUSION: Compared to non-adjuvanted vaccines, Fluad? is cost-effective. Since the estimated cost per life year gained is within acceptable thresholds, Fluad? should be used as the vaccine of choice in older people. * Fluad® is registered under the trade name Gripguard? in France