Background: Surgical treatment modalities of coronary artery diseases (CAD) include on-pump or off-pump coronary artery bypass grafting (CABG). CABG performed on the beating heart can avoid complications that might occur on cardiopulmonary bypass. Our objective was to compare the effectiveness of on-pump versus off-pump CABG in high-risk patients stratified according to the EuroSCORE scoring system. Methods: This randomized clinical study included 80 high-risk patients who underwent CABG and assigned into two groups; each contains 40 patients. Patients with valvular affection, ischemic ventricular septal defect or left ventricle and aortic aneurysms, and/or those exhibiting significant neurological pathology were excluded from the study. Study outcomes were blood loss, length of ICU and hospital stay, inotropic use, re-exploration rate, and operative mortality. Results: The study showed significant higher use of inotropic drugs intra and post-operatively (57.5% vs 40%, p = 0.021), more low cardiac output (12.5% vs 2.5%, p = 0.031), lower blood loss (337±67 vs 498±68 ml, p = 0.01), lower blood transfusion (1.1±0.2 vs 1.2±0.4 unit, p = 0.024), more prolonged ICU stay (4.0±1.6 vs 3.0±0.9 day, p = 0.001) and the higher re-exploration rate (17.5% vs 7.5%, p = 0.035) in the on-pump group. Hospital stay (8.7±2 vs 8.1±1, p = 0.121) and early mortality (7.5% vs 2.5%, p = 0.451) did not differ significantly between the two groups. Conclusion: Management of coronary artery disease is still challenging, and there is still a place for off-pump CABG in CAD in high-risk patients due to its advantages in the early complications while has the same total hospital stay when compared with on-pump CABG.