This study examined the relationship between human patient simulation (HPS), critical thinking skills, and knowledge acquisition after HPS was integrated across the curriculum of an associate degree nursing program to determine if differences existed in critical thinking and knowledge of students based on the fidelity of HPS used and amount of student exposure to HPS. The effectiveness of HPS when used as a teaching strategy in lieu of traditional clinical experiences was examined to determine the impact on critical thinking and knowledge in relation to the percentage of traditional clinical experiences substituted with HPS. The National League for Nurses' (NLN) "Nursing Education Simulation Framework," based on Kolb's experiential learning theory, provided the framework. An ex post facto design was used with a convenience sample of 187 graduates drawn from the six cohorts of graduates who graduated from the nursing program spring 2006 through spring 2010. The Health Education Systems Incorporated (HESI) exit exam's (E[superscript 2]) composite score and HESI E[superscript 2] critical thinking (CT) subscore, used to measure nursing knowledge and critical thinking skills, were compared among the six cohorts of graduates exposed to varying degrees of fidelity and number of hours of traditional clinical experiences substituted with HPS during their educational program. Analysis of variance revealed that a significant difference in knowledge (p = 0.012) existed between the six cohorts. In addition, analysis of covariance revealed that a significant difference in critical thinking skills (p = 0.003) existed between the six cohorts. Polynomial contrasts identified a significant, positive linear trend in HESI E[superscript 2] mean scores (p = 0.001) and HESI E[superscript 2] CT mean scores (p < 0.001) across the six cohorts as exposure to and number of traditional clinical hours substituted with simulation increased. Significant statistical differences existing between pairs of cohorts were identified by pairwise comparisons of the six cohorts. The results supported the use of HPS as an effective teaching strategy in lieu of a small percentage of traditional clinical experiences. No significant statistical differences were identified in knowledge and critical thinking based on the fidelity of HPS used. [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.]