Recent research indicates that there is a high prevalence of heart failure with preserved ejection fraction in patients with peripheral artery disease. We hypothesized that endovascular treatment (EVT) of flow-limiting peripheral stenosis improves left ventricular (LV) diastolic function. Thirty patients with symptomatic peripheral artery disease and heart failure with preserved ejection fraction according to Heart Failure Association-preserved ejection fraction score who were scheduled for EVT or angiography were investigated at baseline, the day after EVT (n=25) or angiography (control, n=5), and at 4 months follow-up. Peripheral hemodynamics were determined by the total peripheral resistance, common femoral artery flow, and ankle brachial index. Aortic function was measured by arterial compliance, augmentation index, and pulse wave velocity. Aortic pulsatile load was estimated as the characteristic impedance of the proximal aorta and the magnitude of wave reflection (reflection coefficient). LV mass index, LV mean wall thickness, and systolic and diastolic function were assessed using echocardiography. Patient-centered outcomes were treadmill walking distance and New York Heart Association class. After EVT, peripheral hemodynamics changed significantly with a decrease in total peripheral resistance and an increase in common femoral artery flow and ankle brachial index. Aortic function improved after EVT, with significantly reduced augmentation index and pulse wave velocity and increased compliance immediately and at follow-up, resulting in a reduction in aortic pulsatile load (characteristic impedance of the proximal aorta and reflection coefficient). Concurrently, LV diastolic function improved after EVT compared with control, acutely and at follow-up, with increased septal and lateral e´ velocities and decreased E/e´ and left atrial volume index. The LV mass index and LV mean wall thickness decreased at follow-up. The New York Heart Association class and treadmill walking distance improved post-EVT at follow-up. Augmentation index, pulse wave velocity, and arterial compliance were identified as independent contributors to E/e´. Endovascular treatment of flow-limiting iliofemoral stenosis reduces aortic pulsatile load and concurrently lowers total peripheral resistance. This beneficial effect is associated with an acute and sustained improvement of left ventricular diastolic function. URL: http://www.clinicaltrials.gov; Unique identifier: NCT02728479.