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Guided by Lent, Brown, and Hackett’s (1994, 2000, 2002) social cognitive career theory, this longitudinal study utilized a matched sample from two national, multi-institutional surveys. This examination aimed to extend the literature on science self-efficacy and to further disentangle the relationship between college experiences and science self-efficacy for first-year STEM students. Findings suggests that male students have higher science self-efficacy than female students at the start and end of their first college year. Furthermore, in-class experiences are stronger predictors of science self-efficacy than out-of-class experiences, yet both positively predict science self-efficacy. Faculty and administrators within STEM departments should consider co-curricular environments that are most effective in building scientific confidence among first-year students, and particularly those environments important to women.