After coronary endarterectomy, patients have an increased incidence of perioperative myocardial infarction. This study was undertaken to evaluate the possible reduction of perioperative myocardial damage after coronary endarterectomy by intravenous utilization of prostacyclin. Elective coronary artery bypass grafting was performed in 1,190 patients with diffuse and distal coronary artery disease, in whom endarterectomy of one or more vessels was used as a treatment. All procedures were done with cardiopulmonary bypass. There were 584 patients in the prostacyclin-treated group, and 606 patients in the control group. Prostacyclin (10 ng · kg −1 · min −1) was started 20 minutes before the cross-clamp removal, or at the time of rewarming, and was continued during the first 24 hours after surgery. The incidence of perioperative myocardial damage was detected by creatine kinase-MB enzyme measurement, and electrocardiographic and left ventricular function changes. A significant decrease in perioperative myocardial damage was detected in the group treated with prostacyclin with respect to the control group. Prostacyclin infusion initiated during revascularization and continued in the early postoperative course could be successfully employed for the prevention of thrombocyte aggregation and potentially decrease the overall incidence of significant myocardial damage after coronary endarterectomy.