Background. Cardiac operations using extracorporeal circulation bear a risk of cerebral complications. The aim of our study was to investigate if off-pump operations without heart-lung machines can reduce cerebral injury. Methods. S100, a protein specific for cerebral tissue, was used as a marker for cerebral impairment in 108 randomized patients undergoing coronary bypass operation: 67 patients (group A) were operated on with extracorporeal circulation and cardioplegic cardiac arrest, and 41 patients (group B) underwent off-pump beating heart revascularization. Both groups were similar regarding age, sex, ejection fraction, and number of anastomoses. S100 levels were measured from induction of anesthesia until 24 hours after the operation. Results. Data collection was 100% complete. There was no in-hospital death. Nonfatal myocardial infarctions occurred in 2 patients in group A, and 1 patient in group B required resternotomy for bleeding. There was no neurologic deficit in either group. S100 levels increased only slightly in the off-pump patients (group B), whereas in group A there was a sharp rise in S100 concentration during extracorporeal circulation, only returning to baseline 6 hours after the end of the operation. Peak S100 levels were four times higher in group A than in group B (2.1 mug/L versus 0.5 mug/L; p < 001). Conclusions. The results of our study suggest that perioperative cerebral impairment is reduced in cardiac operations without the use of extracorporeal circulation. Further large-scale studies are needed to show whether this result is reflected by fewer neurologic deficits. (Ann Thorac Surg 2000;70:1577-9) (C) 2000 by The Society of Thoracic Surgeons.