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Background: Little is known about the best strategy for weaning patients with chronic obstructive pulmonary disease (COPD) from mechanical ventilation. Spontaneous breathing trials (SBT) using a T-piece or pressure-support ventilation (PSV) have a central role in this process. Our aim was to compare T-piece and PSV SBTs according to the duration of mechanical ventilation (MV) in patients with COPD., Methods: Patients with COPD who had at least 48 hours of invasive MV support were randomized to 30 minutes of T-piece or PSV at 10 cm H2O after being considered able to undergo a SBT. All patients were preemptively connected to non-invasive ventilation after extubation. Tracheostomized patients were excluded. The primary outcome was total invasive MV duration. Time to liberation from MV was assessed as secondary outcome., Results: Between 2012 and 2016, 190 patients were randomized to T-piece (99) or PSV (91) groups. Extubation at first SBT was achieved in 78% of patients. The mean total MV duration was 10.82 ± 9.1 days for the T-piece group and 7.31 ± 4.9 days for the PSV group (p < 0.001); however, the pre-SBT duration also differed (7.35 ± 3.9 and 5.84 ± 3.3, respectively; p = 0.002). The time to liberation was 8.36 ± 11.04 days for the T-piece group and 4.06 ± 4.94 for the PSV group (univariate mean ratio = 2.06 [1.29-3.27], p = 0.003) for the subgroup of patients with difficult or prolonged weaning. The study group was independently associated with the time to liberation in this subgroup., Conclusions: The SBT technique did not influence MV duration for patients with COPD. For the difficult/prolonged weaning subgroup, the T-piece may be associated with a longer time to liberation, although this should be clarified by further studies., Trial Registration: ClinicalTrials.gov NCT01464567, at November 3, 2011., Competing Interests: The authors have declared that no competing interests exist.