Claremont Graduate University and San Diego State University: 2018 Nurses serve a valuable role in the healthcare industry. Nurses are trained to have knowledge and skills for a fast-paced, evolving environment. In order to meet the needs of complex and diverse patients, nurses must be able to assess patients and prioritize care to produce safe and quality outcomes. This quantitative study framed in Benner’s Novice to Expert Theory and the National League for Nursing Jeffries Simulation Theory involved undergraduate baccalaureate nursing students from a California State University. The study examined differences in teaching methodologies regarding a low-frequency, high risk patient scenario. Survey responses from 161 participants provided opportunities to identify relationships between various teaching methodologies and nursing student knowledge and skill after a virtual standardized patient (VSP) anaphylaxis simulation. Participating students represented three levels of undergraduate nursing classes. Level one nursing students (Nursing Fundamentals) were familiar with reading case studies but had no formal clinical experience (n = 65). Level two nursing students (Medical-Surgical I) consisted of students with basic clinical experience (n = 60). Level three nursing students (Medical-Surgical II) consisted of students with extensive clinical experience (n = 36). Each willing participant was randomly assigned to a VSP anaphylaxis simulation research group that was delivered by three different teaching methods. Research group one consisted of a video simulation via traditional two-dimensional video plus a written case study (n= 54). Research group two consisted of a three-dimensional, mixed reality VSP simulation via the Microsoft HoloLens® (n = 53). Research group three consisted of a written case study (n =54). Participating students from within the three levels of nursing courses were stratified and randomly assigned to a research group. All students participating in the study received written instructions and an unfolding case study regarding the life threatening disorder of anaphylaxis. Following three observation periods, students were asked a series of knowledge and skill measures. The study participants were largely 19 to 20 years of age, had no previous clinical experience (67.1%), no combined previous immersive simulation experience (60.9%), and varying hours of nursing simulation experience. Correlational statistics showed evidence of a relationship between student knowledge and differences in teaching modalities. A one-way Analysis of Covariance revealed that video instruction provided the most knowledge gained (M= .96) compared to written case study (M = .95), and Microsoft HoloLensÒ. Correlational statistics showed evidence of a relationship between student skill and differences in teaching modalities. A one-way Analysis of Covariance revealed that video instruction provided the most skill (M = .78) compared to the Microsoft HoloLensÒ (M = .69), and written case study (M = .61). Regarding the Microsoft HoloLensÒ group, when looking at overall knowledge, Level 2 (Medical-Surgical I) is the only variable that entered the Stepwise regression model. Regarding the Microsoft HoloLensÒ group, when looking at overall skill, Level 1 (Nursing Fundamentals) is the only variable that entered the Stepwise regression model. The study’s findings showcase the importance of considering which type of teaching modality will provide students an opportunity to gain knowledge and skill when presented with a life-threatening patient scenario. This study suggested video instruction plus a written case study was the teaching modality that provided the most knowledge and skill gained among undergraduate nursing students. These results have significant research, practice, and policy implications for nursing school faculty and administration. In addition, the findings have heuristic value for other healthcare profession educators wishing to use emerging technologies for low-frequency, high-risk scenarios through the use of a virtual standardized patient.