Background Evidence indicates that applying technology to medication safety will improve the quality of medical services and enhance the medication-error management climate. The perceived benefits of using the medication safety system are an important factor for adopting a system. Aims The purpose of this study was to investigate the mediating role of the perceived benefits of using a medication safety system in the relationship between transformational leadership and the medication-error management climate. Methods A total of 153 staff nurses from 11 secondary or tertiary hospitals in Korea were included. Descriptive statistics, t-tests, analysis of variance, Pearson correlations and multiple regression analyses were used. Results Transformational leadership was significantly correlated with the perceived benefits of the system use ( r = .17, p = .032) and medication-error management climate ( r = .55, p < .001). The perceived benefit of using the medication safety system was a mediator between transformational leadership and the medication-error management climate. Conclusions When chief executive officers construct and implement a medication safety system in their hospitals, transformational leadership can enhance the perceived benefits of system use, which is an important factor that contributes to a positive medication-error management climate.