To estimate the economic value of a 'universal' influenza vaccine compared to the standard annual influenza vaccine, starting vaccination in the pediatric population (2-18 year olds), over the course of their lifetime.

Universal vaccine dominates (i.e., less costly and more effective) the annual vaccine when the universal vaccine cost ≤ $100/dose and efficacy ≥ 75% for both the 5- and 10-year duration. The universal vaccine is also dominant when efficacy is ≥ 50% and protects for 10 years. A $200 universal vaccine was only cost-effective when ≥ 75% efficacious for a 5-year duration when annual compliance was 25% and for a 10-year duration for all annual compliance rates. A universal vaccine is not cost-effective when it cost $200 and when its efficacy is ≤ 50%. The cost-effectiveness of the universal vaccine increases with the duration of protection.

Limitations of the current annual influenza vaccine have led to ongoing efforts to develop a 'universal' influenza vaccine, i.e., one that targets a ubiquitous portion of the influenza virus so that the coverage of a single vaccination can persist for multiple years.

Although development of a universal vaccine requires surmounting scientific hurdles, our results delineate the circumstances under which such a vaccine would be a cost-effective alternative to the annual influenza vaccine.

Monte Carlo decision analytic computer simulation model.