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Motivation to study mathematics and science courses is an important predictor of career aspirations in STEM fields. Using a nationally representative sample, the current study identified high school students’ motivation profiles in mathematics and science courses, examined the stability of the profiles, and studied the relationship between motivation profiles and STEM career aspirations. The analysis revealed four distinct motivation profiles at the beginning and end of high school, and the profiles were relatively stable across high school years. Profile membership predicted career aspirations. Students in the high mathematics and high science motivation profile were more likely to aspire for STEM careers and health occupations. Science motivation was a stronger predictor than mathematics motivation of aspirations in health occupations.