Introduction: Spontaneous breathing with a conventional T-tube (TT) connected to the endotracheal tube has been frequently used in weaning from mechanical ventilation (MV), when compared with pressure support ventilation (PSV). However, the acute effects of spontaneous breathing using TT versus PSV on respiratory functional parameters (PaCO2 and SaO2) have not been fully demonstrated. Objective: The purpose of this study was to examine the effects of weaning using spontaneous breathing in TT compared to PSV on respiratory functional parameters in critically ill patients. Method: Twenty-six patients who had received MV for more than 48h and met the inclusion criteria for weaning were assessed. The patients were randomized into 2 groups. first group weaned using TT and second weaned using PSV. Respiratory functional parameters included pressure of carbon diaxoide (PaCO2), peripheral oxygen saturation (SpO2) were measured. Results: PSV mode had statistically significantly lower PaCO2 than TT mode during weaning (P<0.001). Also, PSV mode had statistically significantly higher SaO2 than TT mode during weaning (P=0.007). Conclusion: PSV improves oxygenation and ventilation of patients during weaning from mechanical ventilation.