Background: Heated and humidified high flow nasal cannula (HFNC) oxygen therapy represents a new alternative to conventional oxygen therapy (COT) for hypoxic respiratory failure. However, it has not been evaluated for acute respiratory failure with hypercapnia. Methods: Of a prospective HFNC cohort in medical intensive care unit from April 2011 to February 2013, 18 acute respiratory failure patients with hypercapnia who requiring HFNC oxygen therapy to correct hypoxemia were included. Respiratory variables corrected and arterial blood gases were measured before, 1 hour and 24 hour after applying HFNC, which were compared to during COT. Results: The median age was 72 years (45-85), and 14 (77.8%) patients were male. Acute exacerbation of COPD (55.6%) was the most common reason for oxygen therapy. Baseline PaCO2 was 56.4±12.3 mmHg at admission and 60.5±11.2 mmHg at administration of HFNC. During HFNC, ΔPaCO2 after 1 h and 24 h tended to decrease by -2.0±6.7 and -2.5±8.7 mmHg compared to during COT (1.6±6.5 and 5.2±11.5 mmHg), however, there were no significant difference (p=0.403 and 0.071). Four patients were required invasive mechanical ventilation after HFNC oxygen therapy; however, no one showed aggravated hypercania. Conclusions: After HFNC oxygen therapy, there was no significant increase of the PaCO2 in acute respiratory failure with hypercapnia.Background: Heated and humidified high flow nasal cannula (HFNC) oxygen therapy represents a new alternative to conventional oxygen therapy (COT) for hypoxic respiratory failure. However, it has not been evaluated for acute respiratory failure with hypercapnia. Methods: Of a prospective HFNC cohort in medical intensive care unit from April 2011 to February 2013, 18 acute respiratory failure patients with hypercapnia who requiring HFNC oxygen therapy to correct hypoxemia were included. Respiratory variables corrected and arterial blood gases were measured before, 1 hour and 24 hour after applying HFNC, which were compared to during COT. Results: The median age was 72 years (45-85), and 14 (77.8%) patients were male. Acute exacerbation of COPD (55.6%) was the most common reason for oxygen therapy. Baseline PaCO2 was 56.4±12.3 mmHg at admission and 60.5±11.2 mmHg at administration of HFNC. During HFNC, ΔPaCO2 after 1 h and 24 h tended to decrease by -2.0±6.7 and -2.5±8.7 mmHg compared to during COT (1.6±6.5 and 5.2±11.5 mmHg), however, there were no significant difference (p=0.403 and 0.071). Four patients were required invasive mechanical ventilation after HFNC oxygen therapy; however, no one showed aggravated hypercania. Conclusions: After HFNC oxygen therapy, there was no significant increase of the PaCO2 in acute respiratory failure with hypercapnia.