Background: High-fidelity simulation (HFS) is an interactive and complex experiential learning pedagogy. Given the limited and inconclusive evidence on the effectiveness of HFS in terms of improving student learning outcomes, a more thorough understanding of students' learning experiences and effects of HFS may inform the improvement of nursing training. Purpose: The aim of this study was to examine the learning effectiveness score of HFS, its influencing factors, and the learning experience of nursing students. Methods: A convergent parallel mixed-methods research design was adopted. Five hundred thirty-three third-year undergraduate nursing students completed the Simulation Learning Effectiveness Inventory. Semistructured interviews were used to elicit the opinions of 22 participants regarding their participation in the HFS experience. Results: The quantitative findings showed a moderately high learning effectiveness of HFS among Chinese undergraduate nursing students (121.81 ± 14.93). The learning effectiveness for equipment resources (15.02 ± 2.38), course arrangement (11.18 ± 1.73), and confidence (18.56 ± 3.67) was relatively low. Extroversion and mixed personality (β = 0.14 and 0.10) and “dislike” or “general like” of the course (β = −0.45 and −0.33) were found to influence learning effectiveness (F = 54.79, p < .001, adjusted R2 = .29). In addition, the qualitative findings indicated that the participants felt positively regarding the “debriefing,” “clinical abilities,” and “problem solving” dimensions of the training. Conclusions/Implications for Practice: The focus of the education process and curriculum design of HFS activities should be on improving course arrangement, equipment resources, and students' confidence while paying attention to nursing students' personality traits and course preferences.