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Recently, several articles have suggested that the flipped classroom could be an ideal model for pre-clinical medical education. The flipped classroom approach enables instructor-led time to be dedicated to integration and critical thinking exercises, while students learn foundational material outside of class via online videos or reading assignments. However, few studies have been published on the efficacy of this model for pre-clinical medial students. In this paper, we describe the implementation of a fully flipped classroom in a systems physiology course at The University of North Carolina School of Medicine. The organization of this flipped classroom aimed to keep contact hours and home-study hours equal to the hours previously used in the lecture-based course. With the implementation of the flipped classroom, both student performance on examination and student satisfaction with the course improved slightly compared to those of previous years where the curriculum was primarily delivered by lectures. This paper describes an example of a fully flipped course that demonstrated gains in performance and student course evaluations of a medical school pre-clinical course, and suggests that the flipped classroom could be a useful and successful educational approach in medical curricula.