Background:Obstructive sleep apnea (OSA) is associated with activation of the sympathetic nervous system, and patients with this condition often experience elevated blood pressure (BP), increased BP variability, and nocturnal BP surges.Methods and Results:The SYMPLICITY HTN-3 trial was a large prospective, randomized, blinded, sham-controlled trial of renal denervation for treatment of uncontrolled, apparently treatment-resistant hypertension. In a post hoc analysis, we examined the effect of renal denervation vs. sham control on office and ambulatory (including nocturnal) systolic BP in patients with and without OSA. 26% (94/364) of renal denervation subjects and 32% (54/171) of sham control subjects had OSA. Baseline office and nighttime systolic BP values were similar in both arms, including in subjects with and without OSA. Compared with sham control, renal denervation reduced the 6-month office systolic BP in subjects with (−17.0±22.4 vs. −6.3±26.1 mmHg, P=0.01) but not in subjects without OSA (−14.7±24.5 vs. −13.4±26.4 mmHg, P=0.64), P=0.07 for the interaction between treatment arm and OSA status. In those with sleep apnea, renal denervation was also associated with a reduction in maximum (−4.8±21.8 vs. 4.5±24.6 mmHg, P=0.03) and average peak (−5.6±20.4 vs. 3.2±22.4 mmHg, P=0.02) nighttime systolic BP.Conclusions:OSA subjects appeared to be responsive to renal denervation therapy. However, this hypothesis requires prospective testing.