There is growing evidence showing that outcomes improve when students are involved in an active classroom, as opposed to the more traditional, didactic lecture. One type of active classroom that is becoming more popular is the flipped classroom. A flipped classroom requires students to complete assignments prior to class, so they have exposure to the material that will be covered in the upcoming lecture. Class time is then used to reinforce concepts and answer questions through a variety of activities which require students to be active participants. Despite evidence that shows that students often benefit from participation in an active classroom, most “flipped classrooms” are utilized in low enrollment classes. However, enrollment in anatomy and physiology classes at large institutions often exceeds 100 and can be as high as 900 students. Flipping a large enrollment class presents many logistical hurdles. Thus, the purpose of this study was to see if a flipped classroom could be effectively employed in a large enrollment class, and how this change in classroom format would affect exam scores. We hypothesized that exam scores would be higher in a flipped classroom compared to a traditional, didactic lecture. This study compared the first two exam scores from students enrolled in a 200-level introductory human physiology class during the Fall 2022 and Fall 2023 semesters. The topics for each exam were similar across semesters. The first exam covered core concepts, cell biology and nervous system. The second exam covered nervous system, special senses, and muscular system. The Fall 2022 semester and Fall 2023 had enrollments of 269 and 422 students, respectively. For each semester, students attended four, 50-minute in-person classes, as well as a 110-minute in-person lab. Exams were 50-minutes in length and composed of ~45 multiple-choice questions. While the content and exam set-up were similar between semesters, many exam questions were different between semesters. The Fall 2022 class was taught using a more traditional format, which primarily consisted of didactic lecture, which included active periods where students worked together to answer sample exam questions using TopHat. Students were not required to complete any pre-class assignments, but they did have a weekly, low-stakes formative quiz which helped them assess their understanding of the current week’s topics. The Fall 2023 class utilized a flipped method. Prior to each class, students were expected to watch 2-3 short 8-10 minute videos which were embedded with PlayPosit questions, complete a worksheet with 3-4 questions covering important concepts, and take a 5-question pre-class quiz. Students received points for attending class during both semesters. Students in the flipped classroom (81.7 ± 12.7%) achieved higher Exam 1 scores than those in the traditional classroom (74.0 ± 13.6%, p < 0.001). However, there was no difference in Exam 2 scores between flipped (73.8 ± 13.8%) and traditional classrooms (71.9 ± 16.3%, p = 0.09). Additionally, using TopHat participation as indicator, attendance in the flipped classroom was greater. More students attended the last day of class prior to Exam 2 in the flipped classroom (67%) compared to the traditional classroom (24%). While setting up a flipped classroom requires a lot of upfront work, these findings suggest that a flipped classroom can be successful in a large enrollment class, by increasing student attendance and improving student outcomes. Indiana University, Bloomington Center for Innovative Teaching and Learning; 2023 Summer Instructional Development Fellowship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.