OBJECTIVE To examine whether spironolactone could reduce the severity of obstructive sleep apnea (OSA) and lower blood pressure in patients with resistant hypertension. METHODS This was a blank-controlled, single-center study. Patients with resistant hypertension and moderate-to-severe OSA (apnea-hypopnea index >15 events/h) were enrolled and randomly assigned to the therapy or control group. Patients in the therapy group were administered spironolactone 20 mg once daily (up to 40 mg once daily for 4 weeks, if required) in addition to original antihypertensive medication. Follow-up was 12 weeks. RESULTS Thirty patients were enrolled (n = 15 per group). After 12 weeks of follow-up, apnea-hypopnea index (21.8 ± 15.7 vs. 1.8 ± 12.8, p < 0.05), hypopnea index (9.8 ± 11.1 vs. -2.7 ± 16.8, p < 0.05), oxygen desaturation index (20.8 ± 15.0 vs. 0.3 ± 16.1, p < 0.05), clinical blood pressure, ambulatory blood pressure, and plasma aldosterone level (9.8 ± 6.3 vs. 2.9 ± 6.7, p < 0.05) were reduced significantly in the therapy group compared with the control group. No side effects were reported. CONCLUSIONS Spironolactone reduced the severity of OSA and reduced blood pressure in resistant hypertension patients with moderate-to-severe OSA. These findings may assist in the treatment of OSA in patients with resistant hypertension.