Myocardial areas distal to complete coronary artery occlusions are poorly protected by antegrade cardioplegia. We assessed the effects of coronary sinus cardioplegia in 30 patients undergoing bypass operations and at high risk of cardioplegic maldistribution because of the following anatomical patterns of coronary artery disease: critical (≥50%) stenosis of the left main trunk with total occlusion of the right coronary artery (16 patients) or critical (≥70%) stenosis of the right coronary artery with total occlusion of the left anterior descending (11 patients) or circumflex artery (3 patients). After induction of arrest through the aorta, coronary sinus cardioplegia was given intermittently during the cross-clamp period at a flow rate of 100 mL/min. Intraoperatively, occluded arteries were consistently found to be filled with the retrogradely infused solution. One patient died early postoperatively of low cardiac output and a second patient died later during his hospital stay, presumably of an arrhythmia. At autopsy, none of them had pathological evidence of inadequate myocardial protection. One patient sustained a myocardial infarction and 3 others required inotropes for more than 24 hours postoperatively. Postoperative values for right and left stroke volume indices were not significantly different from prebypass levels. Overall, these results are consistent with the occurrence of limited intraoperative ischemic damage and, by inference, suggest the efficacy of the coronary sinus route in preserving myocardial areas supplied by completely occluded coronary arteries and, hence, in jeopardy of inadequate cardioplegia delivery. © 1991.