We evaluated the advantages of combined antegrade and retrograde GIK cardioplegia in 65 patients undergoing CABG. Thirty seven patients were administered antegrade cardioplegia (Group A), whereas 28 patients were administered combined antegrade and retrograde cardioplegia (Group C). Enzyme release and hemodynamic data were obtained before the onset of CPB and at 1, 3, 6, 9, 12 and 24 hours after operation. Both groups were similar in age and incidence of diabetes, previous MI, PTCA, severity of coronary artery disease and emergent operation. In group A, antegrade cardioplegia produced poor anterior septal cooling in 17 patients (45%). To ensure adequate myocardial protection in these cases 9, patients were anastomosed saphenous vein graft first to LAD instead of IMA and perfused cardioplegic solution through the grafts. In group C, although adequate anterior septal cooling also could not be obtained with antegrade cardioplegia in 16 patients (57%), after retrograde cardioplegia, anterior septal temperature fell below 10 degrees C. The use of IMA graft was more practiced in group C. (79% in group C versus 32% in group A, p < 0.05) Enzyme release (CPK-MB, %CPK-MB, LDH) and hemodynamic data (CI, LVSWI, RVSWI, RVEF, RVEDVI) were similar in both group. Furthermore, no significant difference were noted in the incidence of post-operative LOS, PMI and ventricular arrhythmia. We concluded that the use of combined antegrade and retrograde cardioplegia is more effective than antegrade cardioplegia, because of adequate anterior septal cooling, and it will allow patients with severe and extent coronary artery disease to undergo safe IMA grafting.