Lesbian, gay, bisexual, transgender and queer (LGBTQ) persons face discrimination and bias in the U.S. labor force, with serious consequences for the well-being of this population and for diversity and equality more broadly. Exploratory research suggests that these disadvantages are especially pronounced in science, technology, engineering and math (STEM) environments. To systematically investigate this problem, we propose the first ever national-scale social science study of LGBTQ professionals in STEM workplaces. Using an innovative multi-method research design, we identify particular mechanisms at interactional, organizational, and professional levels that reproduce LGBTQ disadvantage in STEM, and strategies that LGBTQ individuals and groups use to navigate these environments.