Although current research suggests many positive outcomes with the use of high-fidelity simulation (HFS) in nursing education, little is known about the influence of HFS on knowledge retention. This quasiexperimental study examined the effects of HFS on student knowledge acquisition and retention, while validating the simulation quality with established tools on satisfaction, self-efficacy, educational practices, and simulation design. Results indicate that, although HFS had a statistically significant impact on knowledge acquisition, knowledge retention rates were not influenced.