Objective To investigate the safety of high fraction of inspired oxygen (FiO2)during noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)and carbon dioxide (CO2)retention. Methods Fifty-six AECOPD patients with CO2 retention admitted between March 2013 and August 2015 were recruited in the study.All patients received noninvasive ventilation treatment with FiO2<0.5.After stabilization of acute respiratory crisis,FiO2 was increased to 1.0 and lasted for 40 minutes.The changes of tidal volume,respiratory frequency,minute volume,Glasgow coma score,arterial blood gas and SpO2 were observed before and after the FiO2 reset. Results The mean PaO2 increased from (83±14)mm Hg to (165±41)mm Hg and the mean SpO2 increased from (92.4±3.1)% to (97.8±1.9)% significantly (both P<0.001).The mean PaCO2 did not changed obviously from (72±15)mm Hg to (72±14)mm Hg (P=0.438).There were also no significant changes in any of the other parameters. Conclusion During noninvasive ventilation with an FiO2 sufficient to maintain a normal PaO2,an increase in FiO2 does not further increase PaCO2 level in AECOPD patients with CO2 retention.