Background-The objective was to evaluate the effects of aortic annulus size on valve hemodynamics and clinical outcomes in those patients included in the Placement of Aortic Transcatheter Valves (PARTNER) randomized controlled trial cohort A and the nonrandomized continued access cohort. Methods and Results-Patients included the randomized controlled trial (n=574) and nonrandomized continued access (n=1358) cohorts were divided in tertiles according to aortic annulus diameter (small aortic annulus tertile, medium aortic annulus tertile, and large aortic annulus tertile [LAA], respectively) as measured by transthoracic echocardiography. Severe prosthesis-patient mismatch was defined as an effective aortic orifice area of <0.65 cm 2 /m 2 . In the randomized controlled trial cohort, patients in the small aortic annulus tertile who underwent transcatheter aortic valve replacement had a lower incidence of severe prosthesis-patient mismatch (19.7% versus 37.5%; P=0.03) and only a trend toward a higher incidence of moderate-to-severe paravalvular leaks compared with surgical aortic valve replacement (5.7% versus 0%; P=0.06). In the LAA tertile, there were no differences in the rate of prosthesis-patient mismatch between groups, and a significant increase in moderate-to-severe paravalvular leaks was associated with transcatheter aortic valve replacement (9% versus 0%; P=0.01). There were no differences in mortality between transcatheter aortic valve replacement and surgical aortic valve replacement. In the nonrandomized continued access cohort, there were no differences in prosthesispatient mismatch between the small aortic annulus and LAA tertiles, but a higher rate of moderate-to-severe paravalvular leaks was observed in the LAA tertile (5.9% versus 11.5%; P=0.009). Patients in the LAA tertile had a higher mortality rate at 1-year follow-up (P=0.02), and differences persisted in multivariable analysis (P=0.048 for LAA versus medium aortic annulus tertile, P=0.035 for LAA versus small aortic annulus tertile). Conclusions-Aortic annulus size had a major impact on valve hemodynamics and clinical outcomes after transcatheter aortic valve replacement and surgical aortic valve replacement. This study highlights the importance of considering aortic annulus size in the evaluation of high-risk patients who are candidates for aortic valve replacement. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.(Circ Cardiovasc Interv. 2014;7:701-711.)Key Word: aortic valve stenosis