Abstract Introduction Upper airway stimulation (UAS) is recommended treatment for moderate to severe obstructive sleep apnea (OSA) in select patients. Existing data have not focused on gold standard 24 hour ambulatory blood pressure monitor (ABPM) to elucidate the impact of UAS. We hypothesize that UAS reduces ABPM indices characterized using objective sleep-wake from actigraphy data over 12-month follow-up period. Methods A prospective sub-study of the Inspire ® post-approval study at the Cleveland Clinic was designed to examine the effect of UAS on 24-hour ABPM measures post-implantation by examining blood pressure (BP) at baseline, and-2, 6, and 12 months follow-up. Actigraphy data was contemporaneously collected. Paired T-tests were used to evaluate BP changes over time. Repeated measure correlations measured within-patient associations between BP and actigraphy measures. Results Average age and BMI were 62.4 +/-12.9) years and 30.1 +/-3.3 kg/m2, 73.3% males and all Caucasian. The mean baseline systolic, diastolic and mean arterial pressure (MAP) were 119.7+/-12.9 mmHg, 74.3+/-7.4 mmHg and 89.3+/- 8.1 mmHg. There were no changes to number, type or dosage of BP medications. At 12 months, there were non-significant overall mean reduction in systolic [-0.55mmHg, p=0.75], diastolic [-0.73mmHg, p=0.63], and MAP [-0.55mmHg, p=0.71]. Mean sleeping systolic, diastolic and MAP changed by -4.36(p=0.34), -1.45 (p=0.57), -2.18 (p=0.50), respectively. Positive correlations above 0.25 (p<0.10) were observed between all dipping percentage measures and total sleep time. Negative correlations were seen between overall systolic, diastolic and MAP with sleep latency (-0.22, p=0.19, -0.35, p=0.031 and -0.29, p=0.075 respectively). No significant changes in BMI was observed, but average hours of usage decreased over time. Conclusion Although consistent reduction of BP measures were observed post-UAS implantation, findings were not statistically significant. It is unclear whether this is due to insufficient sample size or true lack of effect. Larger-scale clinical and mechanistic studies are needed to enhance understanding of UAS-related vascular influences. Support Funded: Inspire Medical Systems