Objectives: Obstructive sleep apnea (OSA) is a common disease, often treated using continuous positive airway pressure (CPAP) therapy. In many cases, patients fail a CPAP titration study due to inadequate control of the apnea-hypopnea index (AHI, events/hour) or due to treatment-emergent central sleep apnea (TE-CSA). We report our experience using a mode of non-invasive ventilation for alternative treatment of these patients. Material and Methods: We reviewed records of adults who had OSA with AHI >= 15 diagnosed on polysomnography (PSG) with failed CPAP titration and in whom titrations with average volume-assured pressure support (AVAPS) with auto-titrating expiratory positive airway pressure were performed. Results: Forty-five patients, age 57.9 +/- 13.1 y, 26 males, body mass index (BMI) 40.2 +/- 8.7kg/m(2). Reasons for CPAP titration failure included: TECSA (25, 55.6%) and inadequate control of AHI at maximum CPAP of 20cm H2O (20, 44.4%). Changes noted from baseline PSG to AVAPS titration: AHI: 65.3 +/- 29.3 decreased to 22.3 +/- 16.1 (p<0.001). Median time SpO2 <= 88%: 63.7 to 6.9min (p<0.001). In 16 patients the AHI was reduced to <15 and in 16 additional patients the AHI was reduced to <30. Improvement in AHI was not related to gender, age, or opioid use, but was correlated with BMI: Delta AHI=12.2 - (1.4 * BMI); p =0.05. AVAPS resulted in improved sleep architecture: median N3 sleep increased: 1.4% to 19.6% total sleep time (TST) (p<0.001), and median R sleep increased: 6.4% to 13.6% TST (p<0.01). Discussion: For patients with OSA for whom CPAP titration failed, titration with AVAPS may be an effective treatment.