cNEP is a novel treatment for OSA that involves external application of negative pressure over the upper airway via a silicone collar with an integral vacuum source. Previous studies indicate that cNEP reduces apnea-hypopnea index (AHI) during single night polysomnography (PSG). The current study assessed cNEP during 3 weeks of home use. This was a prospective, open label, single arm study in subjects with baseline AHI between 10 and 50/hr (>80% obstructive apneas). The primary efficacy endpoint was an AHI during an observed PSG after 3 weeks of home use (PSG2), where AHI was <15/hr and < 50% of baseline. To qualify, subjects were required to fit one of the two available cNEP collar sizes and to have a successful cNEP titration as defined by an AHI < 15 and < 50% baseline during an in lab PSG (PSG1) where response to two pressures (-25 and -30 cmw) was assessed. Results: 71 subjects (46 males) were enrolled. 23 (36.5%) were treatment naïve. Demographic characteristics included (mean ± S.D.) age 54.6 ± 11; BMI 28.3 ± 4.1; baseline AHI 27.5 ± 11.7. 59 subjects completed PSG1. 27 subjects (46%) exhibited an initial response at PSG1. 16 subjects (64%) exhibited a sustained response at PSG2. An additional 5 subjects had a reduction in AHI, which did not reach the primary endpoint. Compared to baseline, mean AHI was reduced in responders at both PSG1 (6.6 v. 26.7) and PSG2 (7.6 v. 26.7) (p<0.001). Nightly usage of cNEP averaged 4.34 hours. Most subjects and their bed partners preferred cNEP to other OSA treatments. Adverse events consisted mainly of transient local irritation at the collar site. In four subjects, AHI increased from baseline during PSG1 and changed the OSA severity classification in three. Conclusions: cNEP is a safe, effective and well-tolerated intervention during 3 weeks of home use in subjects with moderate and severe OSA. Support: Sommetrics, Inc.