Obstructive sleep apnea is associated with increased cardiovascular morbidity and mortality. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial dysfunction in normotensive subjects with moderate-to-severe obstructive sleep apnea, who were compared with hypertensive and healthy subjects, as well as the impact of continuous positive airway pressure treatment on obstructive sleep apnea subjects. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), cutaneous perfusion responses to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, and circulating endothelial and endothelial progenitor cells in a total of 108 subjects (n=36 each of matched obstructive sleep apnea, hypertension, and healthy cohorts). Subjects with obstructive sleep apnea and hypertension demonstrated abnormal myocardial perfusion (P<0.001 for both comparisons), attenuated brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) compared with healthy individuals. Both hypertensive and obstructive sleep apnea patients showed significant improvements in myocardial perfusion (P<0.01), brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) after 26 weeks of continuous positive airway pressure therapy. There were no significant differences in pulse wave velocity and endothelial cells across the 3 groups. Concomitant endothelial dysfunction and impaired myocardial perfusion are present in otherwise normal subjects with moderate-to-severe obstructive sleep apnea, and effective continuous positive airway pressure treatment reverses many of these macrovascular/microvascular abnormalities.