Gains in knowledge and self-efficacy using human patient simulation (HPS) in the education of prelicensure nursing students have been reported. However, the predictors of improved learning outcomes using this teaching methodology are not known. Using a two-group (participated in HPS, did not participate in HPS), repeated-measures, experimental design, we examined the predictors of higher scores on a Knowledge Questionnaire in 162 students (age = 25.7 ± 6.6, gender = 85.5% female) from four prelicensure cohorts at three nursing schools. Statistical analysis consisted of t-tests, ANOVA and stepwise logistic regression. Covariates included age, gender, learning style, baseline critical thinking, baseline self-efficacy, group membership (control or experimental), and school. Membership in the experimental group was the only statistically significant independent predictor (P < .001) of knowledge gains among the covariates entered into the regression analysis. Members of the control group were two times less likely than those in the experimental group to be in the higher scored group (P < .001), yet this changed once the control group participated in HPS. Our findings show that HPS can independently improve test scores. This study provides evidence that HPS; is an effective teaching methodology for prelicensure nursing students regardless of age, learning style, or critical thinking ability.