BACKGROUND: Few data exist on patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR). Also, very scarce data exist on the usefulness of dobutamine stress echocardiography (DSE) before TAVR in these patients. OBJECTIVES: The authors sought to evaluate clinical outcomes and changes in left ventricular ejection fraction (LVEF) following TAVR in patients with classical LFLG-AS. METHODS: This multicenter registry included 287 patients with LFLG-AS undergoing TAVR. DSE was performed before TAVR in 234 patients and the presence of contractile reserve was defined as an increase of ≥20% in stroke volume. Transthoracic echocardiography was repeated at hospital discharge and at 1-year follow-up. Clinical follow-up was obtained at 1 and 12 months, and yearly thereafter. RESULTS: The median Society of Thoracic Surgeons score of the study population was 7.7% (interquartile range 5.3% to 12.0%), and the mean LVEF and transvalvular gradient were 30.1 ± 9.7% and 25.4 ± 6.6 mm Hg, respectively. The presence of contractile reserve was observed in 45% of patients at DSE. Mortality rates were 3.8%, 20.1%, and 32.3% at 30 days, 1 year, and 2 years, respectively. On multivariable analysis, chronic obstructive pulmonary disease (p = 0.022) and lower hemoglobin values (p < 0.001) were associated with all-cause mortality. Lower hemoglobin values (p = 0.004) and moderate-to-severe aortic regurgitation post-TAVR (p = 0.018) were predictors of the composite of mortality and rehospitalization due to heart failure. LVEF increased by 8.3% (95% confidence interval: 6% to 11%) at 1-year follow-up, and the lack of prior coronary artery bypass graft (p = 0.004), a lower LVEF at baseline (p < 0.001), and a lower stroke volume index at baseline (p = 0.019) were associated with greater increase in LVEF. The absence of contractile reserve at baseline DSE was not associated with any negative effect on clinical outcomes or LVEF changes at follow-up. CONCLUSIONS: TAVR was associated with good periprocedural outcomes in patients with LFLG-AS. However, approximately one-third of LFLG-AS TAVR recipients died at 2-year follow-up, with pulmonary disease, anemia, and residual paravalvular leaks associated with poorer outcomes. LVEF improved following TAVR, but DSE failed to predict clinical outcomes or LVEF changes over time. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS Study]; NCT01835028).