Controversial data exist on clinical outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG-AS) undergoing valve replacement. The objective of this study was to determine the clinical outcomes and treatment futility in patients with paradoxical low-flow (PLF), low-gradient (LG) severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). A total of 493 patients with severe symptomatic AS and preserved ejection fraction (>50%) undergoing TAVI were included. Patients were divided in two groups: high gradient AS group (HG-AS; mean gradient ≥40 mm Hg and stroke volume index >35 ml/m, n = 396); and PLF, LG AS group (PLF-LG-AS; mean AV gradient <40 mm Hg and indexed stroke volume ≤35 ml/m, n = 97). The primary endpoint was treatment futility defined as death or poor functional status (New York Heart Association class III and/or IV) at 6-month follow-up. There were no differences in mortality between groups (PLF-LG-AS: 5%, HG: 8%; adjusted odds ratio (OR): 0.85, 95% confidence interval (CI):0.29 to 2.46), but PLF-LG-AS patients remained more frequently in New York Heart Association class III to IV (20% vs 8% in the HG group, adjusted OR: 2.46, 95% CI:1.19 to 5.07). TAVI treatment futility was more frequent in the PLF-LG-AS group (24% vs 14%, adjusted OR: 1.90 [1.01 to 3.57]), and patients with PLF-LG-AS exhibited a higher rate of rehospitalization for cardiovascular causes (9% vs 5%, adjusted OR: 2.95, 95% CI:1.08 to 8.09). Previous myocardial infarction and chronic obstructive pulmonary disease were associated with treatment futility (p< 0.03 for both). In conclusion, TAVI was a futile treatment in one fourth of patients with PLF-LG-AS. These results underscore the complexity and need for improving the clinical decision-making process and management of patients with PLF-LG-AS.