Purpose: This study aimed to examine the mediating role of nursing professionalism in the relationship between critical thinking disposition and medication safety competency among peri-anesthesia nurses. Methods: Data were collected from 128 peri-anesthesia nurses with at least six months of experience in recovery-related departments across medical institutions nationwide. The analysis was conducted using IBM SPSS Statistics for Windows, version 24.0, including descriptive statistics, t-tests, one-way ANOVA, Scheffé tests, Pearson’s correlation coefficients, stepwise multiple regression, and the SPSS Process Macro. Results: Medication safety competency showed a significant positive correlation with critical thinking disposition (r=.79, p<.001) and nursing professionalism (r=.80, p<.001). Similarly, critical thinking disposition was positively correlated with nursing professionalism (r=.78, p<.001). Nursing professionalism was identified as a partial mediator in the relationship between critical thinking disposition and medication safety competency, with a 95% confidence interval of .11 to .63. Conclusion: Critical thinking disposition significantly enhances medication safety competency, with nursing professionalism serving as a partial mediator. These findings underscore the importance of developing targeted educational programs to foster critical thinking skills and nursing professionalism, ultimately improving medication safety competency among peri-anesthesia nurses.