Objectives: To correlate the degree of encephalopathy, baseline values of PaCO2 and pH, and their early response to NIV with eventual in-hospital outcome in patients of severe acute-on-chronic hypercapnic respiratory failure in COPD. Design: Retrospective review. Setting: Intensive care unit. Material and methods: 24 episodes of acute exacerbation of COPD in 17 patients (10 females, 7 males) with a mean age of 59.5 years (range 48 - 82) where NIV was initiated. Data collected: encephalopathy score at baseline and at 24 hours, respiratory rate, breathing pattern, serial arterial blood gases, duration of NIV support per day and hospital days. Results: All patients had severe hypercapnia (mean peak PaCO2 89.0 mm Hg ± 21; range 66-143), respiratory acidosis (mean nadir pH 7.24 ± 0.058, range 7.14 - 7.33) and tachypnoea (mean respiratory rate 29.5 ± 4.69/mt; range 24 - 40). In 17 episodes, altered mental state was present (encephalopathy score 1.92 ± 1.32, median 2.5). Clinically stable condition occurred over several days (mean 13± 9.6 days; range 5 - 40). Intubation was avoided in 22 out of 24 episodes (91.6%) despite significant initial worsening of PaCO2 and pH. Two patients died. The mean time on NIV was16.5 hours/day (range 4 - 22). Conclusions: In selected patients of COPD with acute hypercapnic failure on NIV worsening PaCO2 and pH in the initial hours may not predict failure provided the level of consciousness and respiratory distress improve.