Background Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation(NPPV),increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure,especially hypercapnic acute respiratory failure(HARF).To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy,a prospective case-control study was conducted at a university respiratory intensive care unit(RICU)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)during the past 3 years.Methods Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups,which were carefully matched for age,sex,COPD course,tobacco use and previous hospitalization history,according to the severity of encephalopathy,22 patients with Glasgow coma scale(GCS)<10 served as group A and 21 with GCS≥10 as group B.Results Compared with group B,group A had a higher level of baseline arterial partial CO2 pressure((102±27)mmHg vs (74±17)mmHg,P<0.01),lower levels of GCS (7.5±1.9 vs 12.2±1.8,P<0.01),arterial pH value(7.18±0.06 vs 7.28±0.07,P<0.01)and partial O2 pressure/fraction of inspired O2 ratio(168±39 vs 189±33,P<0.05).The NPPV success rate and hospital mortality were 73%(16/22)and 14%(3/22)respectively in group A,which were comparable to those in group B(68%(15/21)and 14%(3/21) respectively,all P>0.05),but group A needed an average of 7 cmH2O higher of maximal pressure support during NPPV,and 4,4 and 7 days longer of NPPV time,RICU stay and hospital stay respectively than group B(P<0.05 or P<0.01).NPPV therapy failed in 12 patients(6 in each group)because of excessive airway secretions(7 patients),hemodynamic instability(2),worsening of dyspnea and deterioration of gas exchange(2),and gastric content aspiration(1).Conclusions Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD;a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.