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A substantial proportion of patients with neuromuscular disease (NMD) who undergo positive pressure ventilation via endotracheal intubation for acute respiratory failure fail to pass spontaneous breathing trials and should be considered at high risk for extubation failure. In our study, we prospectively investigated the efficacy of early application of noninvasive ventilation (NIV) combined with assisted coughing as an intervention aimed at preventing extubation failure in patients with NMD.This study is a prospective analysis of the short-term outcomes of 10 patients with NMD who were treated by NIV and assisted coughing immediately after extubation and comparison with the outcomes of a population of 10 historical control patients who received standard medical therapy (SMT) alone. The participants were composed of 10 patients with NMD who were submitted to NIV and assisted coughing after extubation (group A) and 10 historical control patients who were administered SMT (group B), who were admitted to a 4-bed respiratory intensive care unit (RICU) in a university hospital. Need for reintubation despite treatment was evaluated. Mortality during RICU stay, need for tracheostomy, and length of stay in the RICU were also compared.Significantly fewer patients who received the treatment protocol required reintubation and tracheostomy compared with those who received SMT (reintubation, 3 vs 10; tracheostomy, 3 vs 9; P = .002 and .01, respectively). Mortality did not differ significantly between the 2 groups. Patients in group A remained for a shorter time in the RICU compared with group B (7.8 ± 3.9 vs 23.8 ± 15.8 days; P = .006).Preventive application of NIV combined with assisted coughing after extubation provides a clinically important advantage to patients with NMD by averting the need for reintubation or tracheostomy and shortening their stay in the RICU; its use should be included in the routine approach to patients with NMD at high risk for postextubation respiratory failure.