An alternative strategy for pre-exposure rabies vaccination to the institutional recommendations of the World Health Organization and the Centers for Disease Control and Prevention is proposed based on recent long-term follow-up of post-vaccinal seroconversion rates. The alternative strategy uses the same primary series (i.e. vaccination in the deltoid area on D0, D7, and D28), but is completed by a scheduled booster vaccination at D365. The frequency of recommended subsequent booster injections depends on the serological test results obtained by a RFFIT on D379 and 3 years later. The objective of this study was to compare the efficiency of the two pre-exposure strategies. A cost-minimization analysis was carried out to compare the two rabies pre-exposure vaccination and serological test strategies based on the data from two published studies on the long-term evolution of the immunity achieved using the different recommendations. For a theoretically equivalent immunogenicity, the cost of the alternative strategy ranged from 1.7 to 5.2 times lower than that of the institutional recommendations. A sensitivity analysis confirmed the robustness of the results. The alternative strategy should be validated externally under field conditions. This approach would compare its real efficiency to the institutional recommendations.