During the 2012–2013 academic year the University of North Dakota (UND) piloted the use of a Student Centered Active Learning Environment for Undergraduate Programs (SCALE-UP) classroom. Genetics, a 300 level class for Biology majors, and Concepts of Biology, an introductory course for non-majors were two of the classes piloted. Here, we examine the effects of this transition on overall academic performance, grade distribution, exam question performance classified by Bloom’s Taxonomy, student performance by quartile, and University Student Assessment of Teaching (USAT) surveys. Comparisons are made to historical data from a lecture-based setting to examine the effects of switching from an instructor-centered to a learner-centered format. Following the transition, both courses showed a higher proportion of students receiving an A/B/C grade and a concomitant decrease in D/F/W grades, and students continued to have positive perceptions about themselves, the course and the instructor. Paradoxically, both courses experienced a concerning decrease in performance by lower quartile students on comparable exam questions.