Purpose : The Purpose of this study was to identify the physiological, psychological factors to successful weaning of mechanical ventilation in ICU patients. Method: Data was collected by interview with the use of questionnaires from 70 ICU patients, who were mechanically ventilated more than 3days at Y university medical center. Data was analyzed with descriptive statics, t-test, and x² test, and Pearson Coefficient Correlation using SPSS WIN 12.0 program. Result: ICU patients with mechanical ventilator during weaning period reported high levels of anxiety, moderate levels of stress, and fatigue. The physiological, psychological factors influencing ventilator weaning success were RSBI(p=0.007), stress(p=0.009), anxiety(p=0.020), depression(p=0.040), fatigue(p=0.001), and dyspnea(p=0.010). The RSBI factor was shown to have positive correlations with ventilator care periods, Parol, and fatigue, Dyspnea was also positively correlated with stress, anxiety, depression, and fatigue. Conclusion: This study suggests that RSBI, stress, anxiety, depression, fatigue, and dyspnea are significant factors to successful weaning from mechanical ventilation.