Abstract Background Co-existence of moderate aortic stenosis (AS) in patients with heart failure with reduced ejection fraction (HFrEF) is not uncommon. Moderate AS increases afterload, while pharmacological reduction of afterload is a pillar of contemporary heart failure management. Hypothesis Unloading the left ventricle by reducing the trans-aortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate aortic stenosis and HF with reduced ejection fraction. Study Design TAVR UNLOAD ( NCT02661451 ) is an international, multi-center, randomized, open-label, clinical trial comparing the efficacy and safety of TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve in addition to optimal heart failure therapy (OHFT) versus OHFT alone in patients with moderate AS (defined by a mean trans-aortic gradient ≥20 mmHg and <40 mmHg, and an aortic valve area> 1.0 cm2 and ≤1.5 cm2 at rest or after dobutamine stress echocardiography) and HFrEF. A total of 600 patients will be randomized in a 1:1 fashion. Clinical follow-up is scheduled at 1, 6 and 12 months, and 2 years after randomization. The primary endpoint is the hierarchical occurrence of all-cause death, disabling stroke, hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke, and the change in the Kansas City Cardiomyopathy Questionnaire at one year. Secondary endpoints capture effects on clinical outcome, biomarkers, echocardiographic parameters, and quality of life. Summary The TAVR UNLOAD trial aims to test the hypothesis that TAVR on top of optimal heart failure therapy improves clinical outcomes in patients with moderate aortic stenosis and heart failure with reduced ejection fraction.