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The purpose of this study was to determine whether the incidence of postoperative stroke could be reduced by eliminating aortic clamping during coronary artery bypass grafting.From 2002 to 2013, 12,079 patients underwent primary, isolated coronary artery bypass grafting at a single US academic institution. Aortic manipulation was completely avoided by using in situ internal thoracic arteries for inflow in 1552 patients (12.9%) (no-touch), a clampless facilitating device for proximal anastomoses in 1548 patients (12.8%), and aortic clamping in 8979 patients (74.3%). These strategies were assessed in a logistic regression model controlling for relevant variables.The overall incidence of postoperative stroke was 1.4% (n = 165), with an unadjusted incidence of 0.6% (n = 10) in the no-touch group, 1.2% (n = 18) in the clampless facilitating device group, and 1.5% (n = 137) in the clamp group (P < .01 for no-touch vs clamp). The ratio of observed to expected stroke rate increased as the degree of aortic manipulation increased, from 0.48 in the no-touch group, to 0.61 in the clampless facilitating device group, and to 0.95 in the clamp group. Aortic clamping was independently associated with an increase in postoperative stroke compared with a no-touch technique (adjusted odds ratio, 2.50; P < .01). When separated by cardiopulmonary bypass use, both the off-pump partial clamp and the on-pump crossclamp techniques increased the risk of postoperative stroke compared with no-touch (adjusted odds ratio, 2.52, P < .01; and adjusted odds ratio, 4.25, P < .001, respectively).A no-aortic touch technique has the lowest risk for postoperative stroke for patients undergoing coronary artery bypass grafting. Clamping the aorta during coronary artery bypass grafting increases the risk of postoperative stroke, regardless of the severity of aortic disease.