Background: The clinical nursing preceptor system, first introduced in the 1960s, is a one-on-one education and practice model. Preceptorship programs assign experienced registered nurses (preceptors) as mentors or role models for new clinical nurses (preceptees). Purpose: The objective of this study was to delineate the relationship between personality features and teaching self-efficacy in clinical nursing preceptors. Methods: In June 2009, clinical nursing preceptors at a county hospital in Taiwan were asked to complete three questionnaires, including (a) background demographics, (b) Eysenck Personality Questionnaire, and (c) the teaching self-efficacy evaluation. A generalized linear model was applied to determine the associations between the six dimensions of teaching self-efficacy (maturity, teaching self-efficacy beliefs, professional skill, teaching strategy effectiveness, quality of interpersonal relationships, and objective teaching evaluation) and four dimensions related to personality features (extraversion, neuroticism, psychoticism, and the lie scale), adjusted for baseline characteristics. Results: One hundred sixteen nurse preceptors (mean age = 31.2 years, range = 25–54 years) participated in this survey. Analysis showed that extraversion was related to higher scores for maturity, teaching self-efficacy beliefs, professional skill, teaching strategy effectiveness, and objective teaching evaluation. A higher neuroticism score was negatively associated with maturity. The psychoticism score had no significant associations. A higher score on the lie scale was related to lower professional skill and less teaching strategy effectiveness. Conclusions/Implications for Practice: Personality features relate significantly to teaching self-efficacy in nursing preceptors. This study identified personality features that may influence the success of nurses in becoming competent clinical preceptors.