Background. T-piece has been widely used as T-piece trial to identify patients who are ready for extubation but it is seldom used as a weaning tool. Our objective was to investigate the effects of breathing via T-piece on gas exchange as compared to continuous positive airway pressure with pressure support (CPAP+PS) and CPAP with automatic tube compensation (CPAP+ATC) as it has not been evaluated yet. Methods. Tracheostomized, "ready to be weaned" critically ill patients were enrolled in this prospective, auto-control clinical trial. Arterial oxygen tension (PaO2) was determined on CPAP+PS (t(0)), 15 minutes later on CPAP+ATC (t(1)), then on T-piece at 15, 30 and 60 minutes (t(2-4)). ScvO(2) was measured at t(0) and t(4). Settings of fraction of inspired oxygen (FiO(2)) and positive end-expiratory pressure (PEEP) were kept constant throughout the investigation. Results. Twenty-five patients were enrolled. T-piece trial was interrupted in 4 cases after t(2), due to pulmonary oedema, hypertension or fatigue. PaO2/FiO(2) was significantly higher on T-piece (t(3,4)) then on CPAP (t(0,1)), P<0.05, PaO2/FiO(2) did not change significantly on CPAP+PS (t(0)) vs. CPAP+ATC (t(1)) modes: median=208 (interquartile range: 175-266) vs. 223 (186-290) mmHg, P=0.102, but significantly increased from t(0)-t(4): 208 (175-266) vs. 249 (215-325) mmHg, P=0.003, respectively. ScvO(2) was significantly higher on T-piece at t(4): 80% (75-82%) than on CPAP+PS at t(0): 73% (71-78%), P<0.001. Conclusion: On the same FiO(2) and PEEP setting, breathing via T-piece improved oxygenation and resulted in increased ScvO(2) as compared to breathing on CPAP with PS. Our observations suggest a potential role of T-piece during weaning from mechanical ventilation.