The purpose of this study is to develop a simulation-based ventilator training program for general ward nurses and identify its effects. Quantitative data were collected from 29 nurses (intervention group: 15, control group: 14), of which seven were interviewed with focus groups to collect qualitative data. The quantitative results revealed significant differences in ventilator-related knowledge (p = 0.029) and self-efficacy (p = 0.026) between the intervention and control groups. Moreover, three themes were derived from meaningful statements in the qualitative data: understanding psychophysical discomfort of the patient while applying the ventilator; helping in ventilator care; and establishing a future ventilator training strategy. The findings confirmed that the non-invasive positive pressure ventilation (NPPV) simulation program is an effective method for improving the knowledge of ventilator nursing and self-efficacy and will be helpful in developing educational methods and strategies related to ventilator nursing for general ward nurses.