Whereas girls and women outperform men in academic success, men outperform women on vocational success criteria. The present study sought to explain these opposing gender gaps by hypothesizing that, to some extent, different personality traits would promote success in the school and business environments. Using two samples comprised of academic track 11th graders (236) and adult professionals (124), we tested whether gender differences in personality partly explained the opposing gender gaps in academic and vocational success. Questionnaires measuring the Big Five, personality facets, intelligence, and GPA or vocational success criteria were used. Analyses revealed that intelligence, Conscientiousness, and Need for Achievement (AC) predicted both school and vocational success. Agreeableness and Need for Aggression (AG) (negatively) were associated with only academic success. Need for Affiliation (AF) and Need for Dominance (DO) predicted only professional success. Mediation analyses showed that AC, Openness to Experience, Agreeableness, and Conscientiousness (girls scored higher), and AG (girls scored lower) mediated gender differences in academic success. Gender differences in vocational success were mediated by DO (men scored higher), whereas AF (women scored higher) suppressed this relation. The results are discussed with respect to their theoretical and practical implications for understanding gender differences in school and at work.