Rationale: Obstructive sleep apnea syndrome is due to upper airway obstruction and is associated with increased morbidity. While continuous positive airway pressure efficaciously treats obstructive apneas and hypopneas, treatment is impeded by low adherence rates. Objective: To assess the efficacy of a minimally intrusive method for delivering warm and humidified air through an open nasal cannula on obstructive sleep apnea. Methods: Eleven subjects (age 49.7 ± 5.0 years, BMI 30.5 ± 4.3 kg/m²), ranging from mild to severe obstructive apnea-hypopnea syndrome (5 to 60 events / hour) were administered 20 L/min of warm and humidified air through an open nasal cannula Measurements: Standard sleep disordered breathing and arousal indices. In a subset of patients pharyngeal pressure and ventilation was assessed to determine the mechanism of action of treatment with nasal insufflation. Main Results: Treatment with Nasal Insufflation reduced the mean apnea hypopnea index (AHI) from 28 ± 5 to 10 ± 3 events/hour (p < 0.01), and the respiratory arousal index from 18 ± 2 to 8 ± 2 events/hour (p< 0.01). Treatment with Nasal Insufflation lowered the AHI below 10 events/hour in eight of eleven subjects, and below 5 events/hour in four subjects. The mechanism of action appears to be through an increase in end-expiratory pharyngeal pressure, which alleviated upper airway obstruction and improved ventilation. Conclusion: Our findings demonstrate clinical proof of concept that a nasal cannula for insufflating high airflows can be used to treat a diverse group of patients with obstructive sleep apnea.