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Active learning strategies have been previously demonstrated to improve student academic performance across disciplines. The purpose of this study was to determine if flipped classroom improves academic performance among Physician Assistant (PA) compared to a traditional classroom using inter-cohort comparison, and whether prior academic performance and clinical exposure matter. The current data have demonstrated that participation in a flipped-classroom led to significantly greater achievement on standardized assessments following classroom activities after controlling for other important confounding factors. The findings further support the effectiveness of a flipped-classroom setting for didactic level PA students learning medicine.