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Americans with disabilities participate in science, technology, engineering and mathematics (STEM) postsecondary education programs and careers at lower rates than their nondisabled peers. Mentoring has been identified as an approach that may be useful in increasing the number of students with disabilities who choose and pursue STEM areas. A randomized study was conducted to evaluate the impact of mentors on STEM-related self-efficacy, knowledge, engagement, and school performance of high school students with disabilities. Results suggest that experimental group students improved significantly more on measures of these outcomes compared to students in the control group. This is the first random design study of STEM mentoring for youth with disabilities, and only one of two conducted on mentoring of youth with disabilities.