Background Single center studies using serial cerebral diffusion-weighted magnetic resonance imaging in patients having cardiac catheterization have suggested that cerebral microembolism might be responsible for silent cerebral infarct (SCI) as high as 15% to 22%. We evaluated in a multicenter trial the incidence of SCIs after cardiac catheterization and whether or not the choice of the arterial access site might impact this phenomenon. Methods and Results Patients were randomized to have cardiac catheterization either by Radial (n = 83) or Femoral (n = 77) arterial approaches by experimented operators. The main outcome measure was the occurrence of new cerebral infarct on serial diffusion-weighted magnetic resonance imaging. Patient and catheterization characteristics, including duration of catheterization, were similar in both groups. The risk of SCI did not differ significantly between the Femoral and Radial groups (incidence of 11.7% versus 17.5%; OR, 0.85; 95% CI, 0.62-1.16; P = .31). At multivariable analysis, the independent predictors of SCI were the patient's higher height and lower transvalvular gradient. Conclusions The high rate of SCI after cardiac catheterization of patients with aortic stenosis was confirmed, but its occurrence was not affected by the selection of Radial and Femoral access.