Leptospirosis is the most widespread zoonosis in the world. Current vaccines are based on whole-cellpreparations that cause severe side effects and do not induce satisfactory immunity. In light of the leptospiralgenome sequences recently made available, several studies aimed at identification of protective recombinantimmunogens have been performed; however, few such immunogens have been identified. The aim of this studywas to evaluate 27 recombinant antigens to determine their potential to induce an immune response protectiveagainst leptospirosis in the hamster model. Experiments were conducted with groups of female hamstersimmunized with individual antigen preparations. Hamsters were then challenged with a lethal dose of Lepto-spira interrogans. Thirteen antigens induced protective immune responses; however, only recombinant proteinsLIC10325 and LIC13059 induced significant protection against mortality. These results have importantimplications for the development of an efficacious recombinant subunit vaccine against leptospirosis.