Organic Chemistry is a required course for programs in chemistry, biology, and many health science careers. It has historically been considered a highly challenging course with significant failure rates. As with many science disciplines, the teaching of Organic Chemistry has traditionally focused on unstructured exposition-centered delivery of course material. This report details efforts to transform the teaching of a large section of Organic Chemistry to a more student-centered approach through the use of a highly structured, active learning format. In this study, the authors examine student performance data on homogeneous examinations and course grades for two groups of students at a large public university for comparison between those that received highly structured active learning pedagogy and those that received traditional, unstructured, lecture pedagogy in Organic Chemistry. Data consist of repeated cross sections over 4 different years, with a total sample size n = 766. Regression and propensity score matching (PSM) are used to analyze student academic outcomes. Results suggest that students exposed to a highly structured, active learning pedagogy in Organic Chemistry scored statistically significantly higher on total points earned and final exam scores, and had a higher probability of an increase in their final course grade. Results further suggest that while increased structure in conjunction with active learning improved outcomes generally for all students who received it, those students at the lowest academic achievement levels experienced the most gains. This study is significant in its causal analysis of the impact of highly structured active learning on academic outcomes.