There has been a national call to transition away from the traditional, passive, lecture-based model of STEM education towards one that facilitates learning through active engagement and problem solving. This mixed-methods research study examines the impact of a supplemental Peer-Led Team Learning (PLTL) program on knowledge and skill acquisition for students in introductory biology, chemistry, calculus and applied statistics courses. Results indicate program participants reliably outperform their matched pairs in courses that emphasize quantitative reasoning. Moreover, program participants report acquiring important insights about learning, collaboration, and engagement in undergraduate STEM education. These results are consistent with previous findings on PLTL and also provide insight into the roles of course context and student population on program outcomes.