Auto-titrating noninvasive ventilation (NIV) has been developed as a new mode applying variable expiratory-positive airway pressure (EPAP) in addition to variable inspiratory pressures (IPAP), both to deliver targeted tidal volume (VT) and to eliminate upper airway resistance. The purpose of this study is to evaluate whether NIV with auto-titrating mode will decrease more PaCO2 within a shorter time compared to volume-assured mode in hypercapnic intensive care unit (ICU) patients. The hypercapnic respiratory failure patients treated with average volume assured pressure support- automated EPAP mode (group1) were compared with those treated with average volume-assured pressure support mode (group2). Two groups were matched with each other according to baseline diagnoses, demographic characteristics, arterial blood gas values, target VT settings and daily NIV usage times. Built-in software was used to gather the ventilatory parameters. Twenty-eight patients were included in group 1, and 22 in group 2. The decrease in PaCO2 had been achieved within a shorter time period in group 1 (p < 0.05). This response was more pronounced within the first 6 h (mean reduction in PaCO2 was 7 +/- 7 mmHg in group 1 and 2 +/- 5 mmHg in group 2, p = 0.025), and significantly greater reductions in PaCO2 (18 +/- 11 mmHg in group 1 and 9 +/- 8 mmHg in group 2, p = 0.008) and plasma HCO3 levels (from 32 to 30 mEq and from 35 to 35 mEq, p = 0.007) took place within first 4 days. While mean IPAP was similar in both groups, maximum EPAP, mean VT and leak were significantly higher in group 1 than in group 2 (p < 0.05). Results of this preliminary study suggest that, this new auto-titrating NIV mode may provide additional benefit on volume-assured mode in decreasing PaCO2 more efficiently and rapidly in hypercapnic ICU patients.