Background and Objectives: Delay in identifying patients in whom NIV will be unsuccessful may postpone endotracheal intubation, increasing morbidity and mortality. Aim of this study was to determine factors associated with NIV failure in patients with COPD exacerbations. Methods: We retrospectively evaluated COPD patients with acute respiratory failure due to an acute exacerbation, undergoing NIV for at least 12 hours. Univariable analysis was performed on: age, gender, APACHE II, GCS, gas exchange at admission, during NIV and at discharge/death, length of stay. A ROC curve for the variable pH START (arterial pH value at admission) was performed and sensitivity,specificity, likelihood ratios and confidence intervals, were calculated. Results: Among 201 enrolled individuals, NIV failed in 50 subjects, leading to invasive ventilation and/or death. NIV succeeded in patients with: lower APACHE II (20.02±4.81 in succeeding group vs 24.84±6.35 in failing group, p 7.20 and ≤7.25, despite the high percentage of successes observed in this subset of individuals (81%). Conclusion: Further multicentric studies are needed to better define NIV indications, with special reference to pH thresholds.