Abstract Introduction Patients with low-gradient aortic stenosis (mean gradient < 40 mmHg) (LGAS) supose a clinical challenge because in these patients the degree of functional recovery after TAVR could be lower and their prognostic evolution more adverse. This is relevant for the optimal indication of TAVR, especially with the growing number of patients with a borderline indication due to comorbidities or advanced age with certain degree of frailty. Purpose To develop a clinical model to predict the response to TAVR in LGAS patients based in non invasive physiological parameters at baseline. Methods In a cohort of patients undergoing TAVR a prospective evaluation of multiple pathophysiological parameters was performed derived from pre- and post-TAVR assessment with echocardiography, computed tomography, and non-invasive arterial pulse wave analysis with the Sphygmocor XCEL system. Objective functional improvement 6 months after TAVR was assessed by the 6-minute walk test and NT-proBNP levels. Clinical follow-up was performed at 1 year. Results Of the 450 patients included, 310 showed high aortic gradient and 140 (31%) low gradient, with an objective functional improvement in 90% and 64% (p<0.001) respectively, and with 1-year mortality of 4% and 12% (p=0.001). In the LGAS group, 1-year mortality was 20% in the subgroup without functional improvement and 8% (p=0.001) in the subgroup showing functional improvement. In the LGAS group, the pathophysiological parameters predictive of functional improvement were the augmentation index75 ≥ 45% (OR 4, CI 95% 1.9–11.3; p=0.006), posterior wall thickness ≤ 12 mm (OR 3.2, CI 95% 1.4–8; p=0.01) and absence of atrial fibrillation (OR 2.7, CI 95% 1.5–8.4; p=0.01). To generate a simple integer-based point score for each predictive variable, each beta coefficient was divided by the absolute value of the smallest coefficient, multiplied by 5, and rounded to the nearest integer. The values were 7, 6 and 5 respectively. Among the low-gradient population, in 55 patients with 0-6 score points the functional improvement was only 29%, while in the remaining 85 patients with 7-18 score points the functional improvement was 86% (p<0.001). Conclusions LGAS patients account for a relatively high proportion of patients undergoing TAVR. They show less objective functional recovery, which is associated with a significantly higher mortality at follow-up. We have developed a score based on 3 variables (augmentation index75, posterior wall thickness and atrial fibrillation) that can help predict the functional and prognostic response to TAVR in these patients.