The purpose of this study was to determine what the effects of virtual patient simulation instruction are on the learning outcomes of students in an Associate of Science medical-surgical nursing education course. Using a causal-comparative design, this study fills a gap in the literature and adds to the body of knowledge of this instructional strategy to bridge theory to practice in the classroom. Data were acquired from the HESI Exit Examination™, which is administered the last semester of the nursing program. Data were collected for the Summer 2014 through Spring 2016 academic semesters. Additionally, data were acquired from the HESI Mid-Curricular Exam™ during the Summer 2014 through Spring 2015 academic semesters prior to entering the 2nd year of nursing. A post-course “satisfaction with current learning” subsection of the Student Satisfaction and Self-Confidence in Learning survey was administered to assess student satisfaction with the virtual patient simulation. Participants were undergraduate 2nd-year medical-surgical nursing students at one rural public community college. Test scores were collected for students for the 6 semesters from Summer 2014 to Spring 2016. Students who took the course during Fall 2015 and Spring 2016 also completed the satisfaction survey. To be included in the study, students had a grade point average (GPA) of 2.0 or greater in nursing coursework, and had not failed out of the nursing program or the medical-surgical nursing course. Findings revealed no differences between students who received traditional instruction and virtual patient simulation instruction. Satisfaction with the virtual patient simulation instruction was mixed, with the Fall 2015 group being undecided and the Spring 2016 group being satisfied based upon the 5-point Likert-type survey. These results support the hypothesis that virtual patient simulation is comparable to traditional instruction. This study provides evidence that virtual patient simulation is as good as traditional clinical instruction in achieving the student learning outcomes in an associate of science in medical-surgical nursing course.