This study used a quasi-experimental approach with a nonequivalent control group posttest-only design to examine the effectiveness of a virtual escape room on the acquisition of nursing students' knowledge related to leadership nursing content. Additionally, the study measured the students' perceptions of the escape room activity as an effective teaching-learning method using an electronic survey. The study took place during the Fall 2021 semester at a private Catholic college of nursing located in one midwestern state in the United States with two cohorts of students enrolled in a leadership course. One cohort (n = 29) included students from the traditional Bachelor of Science in Nursing program (BSN); a second cohort (n = 21) comprised students from the Second Degree Accelerated Program (SDAP). Following students' participation in the leadership-themed virtual escape room and debriefing session, students were asked to complete an electronic survey evaluating the experience and took a course-required proctored leadership assessment. A comparison of the proctored leadership scores between nursing students who participated in the virtual escape room during Fall 2021 and students' assessment scores from Fall 2020, who did not participate in the virtual escape room, did not demonstrate a statistically significant difference for the SDAP cohorts, and significantly decreased for the traditional BSN cohorts. However, participants perceived the experience as a positive, engaging, and recommendable method for learning. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]