OBJECTIVES: To estimate the cost effectiveness ratio of a inactivated quadrivalent influenza vaccine compared to the trivalent ones in France. METHODS: During some epidemic influenza seasons a mismatch between the circulating B strains and the one included in the trivalent vaccine is observed. The difference of vaccine protection by the quadrivalent vaccine due to the inclusion of both circulating B strains should avoid the occurrence of a number of consultations and complications resulting in hospitalizations and deaths. A decision tree model was built to compare the efficacy and costs of the two vaccines for an average epidemic influenza season in the French setting.  The number of hospitalization and deaths associated with influenza were estimated from an analysis of available French data. Estimates of these medical events were calculated using French standard costs in 2012 and observational data. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: The base case analysis considered the global French vaccinated population during an average epidemic season between seasons 03/04 and 11/12 with a B circulating virus rate of 23% and a mismatch rate of 58%. The perspective is collective. The number of avoided consultations for influenza was estimated at 6,214 and the number of avoided hospitalizations and deaths at 614 and 372 respectively. The number of life years gained (LYG) was estimated at 5,382. The cost per LYG was estimated at 3,138€/LYG. Sensitivity analyses showed clearly the importance of the B circulating virus rate combined with the mismatch rate highly variable according to influenza seasons. PSA showed that 100% of estimates in the acceptability curve were under 20,000€ per LYG in the base case analysis. CONCLUSIONS: The cost effectiveness ratio of an inactivated quadrivalent influenza vaccine compared to trivalent ones in the French setting can be considered acceptable.