Study Objectives: Patients with obstructive sleep apnea syndrome (OSAS) using continuous positive airway pressure (CPAP) often report pressure-related discomfort. Both lower pressure and increased comfort may improve patients' compliance with CPAPtherapy, thereby improving therapeutic effectiveness. Combining CPAP with an oral appliance (hybrid therapy) could be an adequate alternative therapy.Methods: Seven patients with moderate to severe OSAS who tolerated their CPAP despite high pressures (≥ 10 cm H2O) were fitted with hybrid therapy. The mandible was set at 70% of patient's maximum protrusion, and CPAP pressure was set at 6 cm H2O. When OSAS complaints persisted, pressure was increased. After 3 months, a polysomnographic study was performed. At baseline (conventional CPAP) and after 3 months (hybrid therapy) patients filled in questionnaires assessing comfort, compliance, and satisfaction with treatment, excessive daytime sleepiness, and quality of life.Results: Four of seven patients reported hybrid therapy to be more comfortable and effective and preferred it over conventional CPAP. There were no differences between baseline (conventional CPAP) and follow-up (hybrid therapy) scores in compliance, satisfaction, daytime sleepiness, and quality of life. Effectiveness of hybrid therapy was good as apnea-hypopnea index (AHI) significantly decreased from median AHI 64.6/h (interquartile range [IQR] 31.0-81.0) at diagnosis to median AHI 1.5/h (IQR 1.0-33.4) with hybrid therapy. There was no statistical difference in effectiveness between conventional CPAP and hybrid therapy (median AHI with conventional CPAP was 2.4/h [IQR 0.0-5.0]). Conclusions:Although pressure could be lowered and hybrid therapy seems a comfortable alternative to conventional CPAP, there were no differences between both therapies regarding compliance, satisfaction, and both objective and experienced effectiveness. Combined therapy is feasible in OSAS and should now be investigated in a RCT including assessment of comfort and long-term compliance.