Background: Cardioplegia is used to protect the heart from ischemic insult. In left main coronary artery disease, free and homogenous spread and chemical preservation of antegrade cardioplegia is limited. Other option is to bypass the left main stenosis by giving retrograde cardioplegia. Objective: This study aimed to compare the postoperative cardiac function, and clinical outcome between antegrade and retrograde blood cardioplegia in left main coronary artery disease patients who underwent CABG. Patients and methods: A randomized retrospective observational comparative study that was done in Beni-Suef University. The study included 40 patients with left main coronary artery disease who had elective isolated on pump CABG between June 2017 to June 2022, of them 20 patientshad antegrade cardioplegia and the other 20 had retrograde cardioplegia. Results: There was no statistical significance difference between both groups regarding patients' demographics, baseline clinical data, preoperative investigations, operative and postoperative data, except in more inotropic support usage (P value 0.024) and more post-operative elevation of cardiac enzymes (P value 0.028) in antegrade cardioplegia group. Regarding postoperative morbidities there was no statistically significant difference between both groups. Also, there was no complication form retrograde cardioplegia cannula and no mortality in our study group. Conclusions: There is no difference between antegrade and retrograde cardioplegia in left main coronary artery disease patient who underwent CABG except for higher rate of postoperative elevation of cardiac enzymes and more patients required inotropic support with antegrade cardioplegia, without any difference in the incidence rate of postoperative morbidity and mortality between both groups.