Objectives: The aim of this study was to assess the relationship of the severity of myocardial dysfunction to the severity of sleep apnea syndrome (SAS) in patients with drug-resistant hypertension. Methods and Results: Thirty-five patients with drug-resistant hypertension underwent complete overnight polysomnography and comprehensive echocardiography including Doppler tissue imaging and speckle tracking analysis within 24 hours. Severe SAS was defined by the presence of severe SA-induced hypoxemia as indicated by percentage of sleep time with oxygen saturation < 90% (t90)>/= 12%. Heart failure with normal ejection fraction (HFNEF) and t90 >/= 12% were found in 66% and 31% of subjects, respectively. Multivariate regression analysis revealed a significant and independent association of left atrial volume index (LAVI) with t90 >/= 12% (OR 1.292, CI 1.041-1.604, p = 0.020). Severe SA-induced hypoxemia was found in 11 (48%) patients with HFNEF, but in none of those without HFNEF (p < 0.01). Conclusion: In patients with drug-resistant hypertension, there exists a significant association of diastolic dysfunction and heart failure with severe SAS. LAVI represents an independent predictor of severe SA-induced hypoxemia.