Clinically appropriated and procedurally correct hand hygiene is performed less than 50% of the time by health professionals resulting in suboptimal patient care. The use of serious simulation games has been suggested to provide emerging health professional students the opportunity to practice proper hand hygiene behaviors to individualized, dose-sufficient mastery. The purpose of this study was to conduct early efficacy testing of a Hand Hygiene Serious Simulation Game (HH-SSG), which was learner-centrically designed to motivate non-game-oriented grade, college-bound, female health science students to independently persistent in playing to a Level III win state. Eleven of 15 students (73.33%) who played the game chose to advance to the Level III win state. Nine of these students (81.82%) reported that they did not play games very often or they never played games. These students ranked "Realistic Physical Environment," "Relevant Clinical Performance Tasks," and "Not Spreading an Antibiotic Resistant Infection" as the most motivating design elements of the HH-SSG. Pre post hand hygiene knowledge assessment scores significantly improved and were retained for Level III achievement students. Most significantly, pre post perception of cost (perceived effort) decreased significantly for these students while perceived value and achievement motivation remained stable. These results are promising and suggest that non-game-oriented female emerging health professional students may be willing to persist in playing a more accessible HH-SSG to individualized, dose-sufficient mastery beyond the fixed curricular constraints of traditional education settings. [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://www.proquest.com/en-US/products/dissertations/individuals.shtml.]