Using a biopsychosocial model of challenge and threat, we tested resting heart rate variability (HRV) as a moderator of physiological reactivity after experiencing sexism. Women science, technology, engineering, and mathematics (STEM) majors participated in a mock interview in which the male interviewer made a sexist or neutral comment. Resting HRV moderated physiological stress reactivity among women in the sexism condition, but not control, indicating lower resting HRV predicted greater physiological threat than challenge and higher resting HRV predicted greater physiological challenge than threat during the interview. These findings support the emotion regulation properties of HRV as applied to a biopsychosocial model of challenge and threat. Higher resting HRV may be adaptive for women experiencing sexism in male-dominated contexts like STEM.