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Calculus, the study of change in processes and systems, serves as the foundation for many STEM disciplines. Traditional, lecture-based calculus instruction may present a barrier for students seeking STEM degrees, limit their access to STEM professions, and block their potential to address society’s challenges. A large-scale pragmatic trial with randomized student allocation was conducted to compare two calculus instruction styles: active student engagement (treatment condition) versus traditional, lecture-based instruction (control condition). A sample of 811 university students were studied across 32 sections taught by 19 instructors over three semesters at a large, US-based Hispanic-serving institution. Large effect sizes were consistently measured for student learning outcomes in the treatment condition, which demonstrates a new standard for calculus instruction and increased opportunities for completion of STEM degrees.