SUMMARY: The shift to online learning due to the COVID-19 pandemic sheds light on the need for innovative approaches to medical education, making it more interactive and effective. Histology is a challenging subject because it is known to be image intensive. In this study, we compared two methods of online teaching of practical histology: an interactive method using the Poll Everywhere Audience Response System and a traditional method without the use of Poll Everywhere. We performed a randomized controlled crossover trial. One hundred and forty students were divided into two groups. The first group was taught using the interactive method and the second group was taught using the traditional method. Each group was then taught using the other method for a second subject. Students’ performance and preferences were assessed using tests and questionnaires. The examination scores were significantly higher for Poll Everywhere group. All students’ responses were overwhelmingly in favor of the use of Poll Everywhere, with regard to their engagement, enjoyment, and morphology understanding, in addition to the applicability of the interactive approach. Interactive sessions of practical histology using applications such as Poll Everywhere can be an effective way to increase students’ engagement, enjoyment, and knowledge retention during distance learning.