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In coronary artery bypass grafting (CABG) patients, neuropsychological deficits that are present from the time of the operation through 6 months postoperatively are considered permanent and represent organic brain damage related to the operation. We hypothesized that changes in our surgical method would reduce persistent deficits.From 1999 to 2004, consenting CABG patients were randomly assigned to multiple aortic cross-clamp or single aortic cross-clamp technique. An additional contemporary group of patients treated with off-pump CABG was studied. All patients underwent an 11-part neuropsychologic examination preoperatively, and at 1 week, 6 weeks, and 6 months postoperatively. One hundred seven patients with no postoperative neurologic deficits had neuropsychologic examinations at all four testing periods.Off-pump CABG patients were significantly younger (60 ± 11 years) than multiple aortic cross-clamp (66 ± 8 years) and single aortic cross-clamp (64 ± 9 years; p < 0.05) patients. At 6 months, 26% of 27 multiple aortic cross-clamp patients had neuropsychological deficits, 27% of 26 off-pump CABG patients had neuropsychological deficits, and only 9% of 54 single aortic cross-clamp patients had neuropsychological deficits (p = 0.067 versus multiple aortic cross-clamp and off-pump CABG).These results suggest that surgical technique is very important in determining cognitive outcome after CABG. Cardiopulmonary bypass is not the most important factor in determining outcome and when carefully performed with single cross-clamp and minimal aortic manipulation is equal or may be superior to off-pump operation. We suspect that mild hypothermia in on-pump surgery is additionally neuroprotective, a factor that should be taken into account when planning an operation.