Prospectively to investigate the efficacy of non-invasive positive pressure ventilation (NPPV) combined with cricothyroid "mini-tracheostomy" (CM) as a first-line intervention in patients with acute respiratory failure (ARF) of neuromuscular origin, in comparison with positive pressure ventilation (PPV) via endotracheal intubation (ETI).Prospective analysis of the short-term outcomes of 14 non-consecutive patients suffering from ARF of neuromuscular origin who were administered NPPV and comparison with the outcomes of 14 matched historical control patients receiving conventional mechanical ventilation (MV) via ETI.Adult five-bedded respiratory intensive care unit in a university hospital.Fourteen neuromyopathic patients who developed hypercapnic ARF and were submitted to NPPV (group A) and fourteen matched historical control patients, who were administered PPV via ETI (group B). Seven subjects receiving NPPV also underwent CM.Mortality during ICU stay and treatment failure were evaluated; treatment failure was defined as death or the need for ETI for the NPPV group and as death or the inability to wean from MV for the control group. Length of stay in the ICU and time to improvement, defined as the time required for a significant relief of dyspnea and neurologic impairment and for correction of arterial blood gases, were also compared.Intra-hospital mortality and treatment failure were lower in the NPPV group than in the conventional PPV via ETI group (2 vs 8 cases and 4 vs 11 cases, respectively). In addition, the duration of ICU stay for subjects who underwent NPPV was shorter than for patients who were intubated (13.6 +/- 9.7 vs 47.1 +/- 51.9 days). "Mini-tracheostomy" was well tolerated and no significant side effects were encountered. Two patient were excluded from the study because they showed a severe inability to swallow and needed to be intubated to protect the upper airway from the risk of aspiration.Non-invasive positive pressure ventilation in combination with CM may be considered as a safer and more effective alternative to ETI in the treatment of patients with neuromuscular disorders (NMD) who develop ARF and require MV; nevertheless, patient selection remains important, since a significant proportion of neuromyopathic patients might have to be excluded from NPPV because of severe risk of aspiration.