BACKGROUND The flipped classroom model for didactic education has recently gained popularity in medical education; however, there is a paucity of performance data showing its effectiveness for knowledge gain in graduate medical education. OBJECTIVE We assessed whether a flipped classroom module improves knowledge gain compared with a standard lecture. METHODS We conducted a randomized crossover study in 3 emergency medicine residency programs. Participants were randomized to receive a 50-minute lecture from an expert educator on one subject and a flipped classroom module on the other. The flipped classroom included a 20-minute at-home video and 30 minutes of in-class case discussion. The 2 subjects addressed were headache and acute low back pain. A pretest, immediate posttest, and 90-day retention test were given for each subject. RESULTS Of 82 eligible residents, 73 completed both modules. For the low back pain module, mean test scores were not significantly different between the lecture and flipped classroom formats. For the headache module, there were significant differences in performance for a given test date between the flipped classroom and the lecture format. However, differences between groups were less than 1 of 10 examination items, making it difficult to assign educational importance to the differences. CONCLUSIONS In this crossover study comparing a single flipped classroom module with a standard lecture, we found mixed statistical results for performance measured by multiple-choice questions. As the differences were small, the flipped classroom and lecture were essentially equivalent.