ABSTRACT Black, Latinx, American Indigenous, and Pacific Islander students remain underrepresented in biomedical majors and research careers. Some of this problem is because science courses and careers are presented in ways that do not align with aspects of URM students’ social identities and values. URM students (particularly female URM students) feel like they do not belong or are “imposters” in science, especially when compared to well-represented (WR) white and Asian students (particularly male WR students). Bolstering student agency is a promising and innovative strategy that could address these issues. Nascent but growing correlational and experimental research suggests that supporting students’ orientation for agency has the potential to shift aspects of student motivation for science and subjective experience in science classes, as well as instructors’ practice and classroom climate, bringing the science education that URM students are provided into alignment with their goals and identities. The purpose of this investigation is to examine the effectiveness of an intervention designed to promote an agentic orientation among diverse college students in introductory classes required in biomedical science majors. A longitudinal, cluster-randomized, active control experiment (N~90 classes and 6,750 students) across multiple universities will be conducted to test the hypothesis that an intervention promoting an agentic orientation (i.e., training students to adopt a malleable mindset of their science motivation and classroom environment and use a variety of agentic engagement strategies) supports students’ initial persistence and achievement in biomedical science via psychological and environmental processes (Aim 1), as well as their sustained persistence and achievement up to 4 years following the start of the intervention study (Aim 2). Persistence and achievement outcomes include course grades, GPA, course- taking, biomedical degree obtainment, and career/graduate program intentions. Proximal process variables include reports of students’ agentic mindset, engagement, interest, psychological needs, self-efficacy, identity, perceived belonging, imposter beliefs, and empowerment, as well as classroom motivating climate reports and observations. The inclusion of a condition combining the student-focused agentic orientation intervention with a training intervention for science instructors on encouraging students’ agency, autonomy, and motivation will provide the opportunity to examine the added benefit of training teachers over and above the benefits of the student-focused intervention alone (Aim 3). Finally, this large, well-powered intervention study will allow for testing of the hypothesis that an agentic orientation intervention will be equally or more effective for URM vs. WR students and exploration of the extent to which intervention effects vary depending on other characteristics of students (e.g., gender, first-generation, personality, v...