Here we describe a 4-yr course reform and its outcomes. The upper-division neurophysiology course gradually transformed from a traditional lecture in 2004 to a more student-centered course in 2008, through the addition of evidence-based active learning practices, such as deliberate problem-solving practice on homework and peer learning structures, both inside and outside of class. Due to the incremental nature of the reforms and absence of pre-reform learning assessments, we needed a way to retrospectively assess the effectiveness of our efforts. To do this, we first looked at performance on 12 conserved exam questions. Students performed significantly higher post-reform on questions requiring lower-level cognitive skills and those requiring higher-level cognitive skills. Furthermore, student performance on conserved questions was higher post-reform in both the top and bottom quartiles of students, although lower-quartile student performance did not improve until after the first exam. To examine student learning more broadly, we also used Bloom’s taxonomy to quantify a significant increase in the Bloom’s level of exams, with students performing equally well post-reform on exams that had over twice as many questions at higher cognitive skill levels. Finally, we believe that four factors provided critical contributions to the success of the course reform, including: transformation efforts across multiple course components, alignment between formative and evaluative course materials, student buy-in to course instruction, and instructional support. This reform demonstrates both the effectiveness of incorporating student-centered, active learning into our course, and the utility of using Bloom’s level as a metric to assess course reform.