We examined perfectionistic personality characteristics and their association with science self-efficacy beliefs and academic performance among college students in science, technology, engineering, and mathematics (STEM). We were especially interested in gender differences in effects given that women remain significantly underrepresented in several STEM areas. Participants were a large sample of undergraduate students (N = 450; 52% women) majoring or intending to major in a STEM field. Science self-efficacy and course grades were the main outcome variables; high school GPA was a covariate. Latent profile analyses based on measures of perfectionism and personality (conscientiousness, neuroticism) supported a three-class model of perfectionism. Perfectionism for men was not substantially associated with self-efficacy or grades. Although perfectionism also was not associated with self-efficacy for women, maladaptively perfectionistic women did perform significantly lower in their STEM-related courses compared with other groups. Results indicated that maladaptively perfectionistic women may be at risk for performance disappointments in STEM courses where women have traditionally been under-represented. In contrast, adaptively perfectionistic women are strong academic performers in those courses. Intervention efforts aimed at addressing the so-called "leaky pipeline" might want to account for perfectionism and its adaptive and maladaptive implications for women pursuing STEM careers. (Contains 5 tables.)