There is a critical need for faculty, a shortage of clinical sites, and an emphasis on quality and safety initiatives that drive increasing use of simulation in nursing education. Debriefing is an essential component of simulation, yet faculty are not consistently prepared to facilitate it such that meaningful learning, demonstrated through clinical reasoning, occurs from the experience. The purpose of this exploratory, quasi-experimental, pre-test-post-test study was to discover the effect of the use of a simulation teaching strategy, Debriefing for Meaningful Learning (DML), on the development of clinical reasoning in nursing students. Clinical reasoning was measured in 238 participant students from a Midwestern university school of nursing taking an adult health course that uses simulation. Participants were assigned to either the experimental or control group where the DML was compared to customary debriefing using the Health Sciences Reasoning Test (HSRT) before and after the debriefing experience, and the Debriefing Assessment for Simulation in Healthcare©–Student Version (DASH©–SV) with four supplemental questions about the DML (DMLSQ) process, during the post-debriefing assessment. This research sought to understand if the DML debriefing strategy positively influenced the development of clinical reasoning skills in undergraduate nursing students, as compared to usual and customary debriefing. The data revealed that there was a statistical difference between total mean test scores measured by the HSRT. There was, additionally, statistical significance in the change in scores between pre-test and post-test for those who used the DML as compared to the control. There was also a difference in the student’s perception of the quality of the debriefing measured by the DASH©–SV with the DML rated statistically higher than usual debriefing. Finally, there was a significant correlation, demonstrated through regression analysis, between the change in HSRT scores and students’ perception of quality debriefing and the use of the DML. This study contributes to the growing body of knowledge about simulation pedagogy, provides tools for use in debriefing, and informs faculty on best practices in debriefing.