BACKGROUND Randomized controlled trials (RCTs) have shown that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) reduces blood pressure (BP). CPAP treatment has never been compared with antihypertensive medications in an RCT. OBJECTIVE To assess the respective efficacy of CPAP and valsartan in reducing BP in hypertensive patients with OSA never treated for either condition. METHODS In this 8-week randomized controlled crossover trial, 23 hypertensive patients (office systolic BP/diastolic BP: 155 ± 14/102 ± 11 mm Hg) with OSA (age, 57 ± 8 yr; body mass index, 28 ± 5 kg/m(2); apnea-hypopnea index, 29 ± 18/h) were randomized first to either CPAP or valsartan (160 mg). The second 8-week period consisted of the alternative treatment (crossover) after a 4-week washout period. RESULTS Office BP and 24-hour BP were measured before and at the end of the two active treatment periods. Twenty-four-hour mean BP was the primary outcome variable. There was an overall significant difference in 24-hour mean BP between treatments: the change in 24-hour mean BP was -2.1 ± 4.9 mm Hg (P < 0.01) with CPAP, and -9.1 ± 7.2 mm Hg with valsartan (P < 0.001), with a difference of -7.0 mm Hg (95% confidence interval, -10.9 to -3.1 mm Hg; P < 0.001). The difference was significant not only during daytime but also during nighttime: the change in nighttime mean BP with CPAP was -1.3 ± 4.6 mm Hg (not significant), and -7.4 ± 8.4 mm Hg with valsartan (P < 0.001), with a difference of -6.1 mm Hg (P < 0.05) (95% confidence interval, -10.8 to -1.4 mm Hg). CONCLUSIONS In an RCT, although the BP decrease was significant with CPAP treatment, valsartan induced a fourfold higher decrease in mean 24-hour BP than CPAP in untreated hypertensive patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT00409487).