Purpose: : This study aimed to assess the effectiveness of an advanced practice nurse (APN)-driven ventilator weaning protocol for patients undergoing cardiac surgeries. Methods: : A retrospective analysis was conducted on 226 patients admitted to the intensive care unit (ICU) of a tertiary hospital between January and June 2020, following a cardiac surgery. Patients were divided into an APN protocol-applied group (experimental group, n=152) and a control group managed based on doctors' judgment (n=74). Ventilator weaning criteria and clinical outcomes, including duration of ventilation, length of ICU stay, and rate of reintubation, were compared between the two groups. Results: : Patients in the control group were older and had a higher incidence of massive bleeding from chest tube drainage (＞100 cc/hr) at baseline. The average duration of ventilation was significantly shorter in the experimental group compared to the control group (7.44 vs. 21.61 hours, p ＜.001). Furthermore, the mean length of ICU stay was shorter in the experimental group compared to the control group (47.96 vs. 77.97 hours, p ＜.001). There was no difference in the rate of reintubation between the two groups. Conclusion : These findings suggest that an APN-driven ventilator weaning protocol can improve clinical outcomes without significant complications. These results support the adoption of APN-driven mechanical ventilator weaning protocols in clinical practice.