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Background: Nursing education influences medication administration practices, which involve clinical decision making and risk perceptions. Method: This mixed-methods concurrent nested study explored the relationship among knowledge, personality traits, and self-efficacy related to medication administration error in fourth-year, prelicen-sure nursing students ( n = 60) who were recruited from three campuses of a large university. Results: Results indicated low mean knowledge (70.75) and neuroticism (2.44) scores, and high mean self-efficacy and confidence (5.78) and conscientiousness (4.51) scores. Conscientiousness was correlated with both knowledge ( r = .271, p = .036) and neuroticism (r = −.313, p = .015). Thematic analysis yielded four themes: nature of risk perceptions, more opportunities to learn, experiences with medication administration error, and intrinsic characteristics influence errors. Convergence was evident in both knowledge and personality data; self-efficacy/confidence and risk perceptions data diverged. Conclusion: Knowledge, personality traits, and self-efficacy appear to influence nursing students' risk perceptions of medication administration error, indicating an area for future research. [ J Nurs Educ . 2022;61(7):367–374.]