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This study investigated high-achieving students’ persistence in STEM fields using nationally representative data from the High School Longitudinal Study of 2009. The results indicated that approximately 70% of high-achieving students continued their initial STEM degrees within 3 years of college enrollment. We used machine learning techniques and methods in our analyses. The results revealed that the most important predictors of STEM persistence were: math proficiency level, school belonging, school engagement, school motivation, school problems, science self-efficacy, credits earned in computer sciences, GPA in STEM courses, credits earned in STEM courses, and credits earned in Advanced Placement/International Baccalaureate (AP/IB) courses. Math proficiency was the most important variable in the study. Machine learning methods used in the study provided good accuracy.