Purpose: This study attempted to enhance the nurses’ safety competence in administering medications by using simulation training focused on high-alert medication. Method: A total of 30 nurses from 14 teams participated in the simulation training using a high-fidelity patient simulator. Medication administration performance and built-in error recovery was observed using a medication administration safety assessment checklist. Medication safety knowledge and confidence were measured before and after simulation training. Data were analyzed using descriptive statistics and a paired t-test. Results: There were numerous variations in safe medication administration. The safety behavior by oral prescription was insufficient compared to that by routine medication prescription. Following simulation training, knowledge of medication safety increased significantly, but confidence did not. Conclusion: Nurse educators may consider simulation to be an effective strategy for enhancing nurses’ medication safety competence.