AIMS The purpose of the present study was too explore the role of interatrial dyssynchrony in heart failure with preserved ejection fraction (HFPEF). METHODS AND RESULTS For the case study we selected seven patients with severe HFPEF, with interatrial block on electrocardiogram (ECG), and a delayed and interrupted A wave on mitral Doppler. Echocardiographic left atrial (LA) volumes/functions, mitral E/A and E/e' ratios, mitral A wave duration/deceleration time, and interatrial mechanical delays (IAMDs) at tissue Doppler, were studied. We performed right heart catheterization, and an electrophysiological study (EPS) for the measurement of interatrial conduction delay (IACD) and left atrioventricular interval (LAVI). Mean IAMD was 106 ms. All the patients exhibited a restrictive mitral Doppler pattern, high E/A and E/e' ratios, and short A wave duration/deceleration time. Left atrial volume was increased, with severely depressed functions. Right heart catheterization showed severe post-capillary pulmonary hypertension. The EPS showed an IACD of 170 ± 20 ms, with a short LAVI. Left atrial pacing through the coronary sinus reduced the IACD to 25 ± 15 ms. In the pilot study, 29 patients with HFPEF were compared with 27 age-matched control patients. HFPEF patients had longer P waves, shorter A waves, and a longer IAMD than the controls. Prevalence of severe IAMD >60 ms was 59% in HFPEF and 0% in controls. In the HFPEF group, patients with an IAMD >60 ms had significantly shorter A waves and higher E/e' ratio. CONCLUSION Some HFPEF patients present with IACD, delayed LA systole, shortened LA emptying, decreased LA compliance, and increased filling pressures. Whether the condition of these patients could be improved by atrial resynchronization deserves further investigation.