Background: This study aims to compare the operative and postoperative results of on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass surgery (CABG) for multi-vessel coronary revascularization (≥4 anastomoses). Methods: From May 2018 to August 2019, a total of 120 patients (22.5% women, mean age 61.5±8.4 years) received either ONCAB (Group 1, n=60) or OPCAB (Group 2, n=60) for multi-vessel coronary artery disease (CAD). Preoperative left ventricular (LV) ejection fraction (EF) was 53.1%±8.4%.Median EuroSCORE II was 1.59 (interquartile range, 1.01-2.54). The median number of performed coronary anastomoses was 4 (interquartile range, 4-5), with equal distribution in both groups (P=0.4). All procedures were performed by highly experienced surgeons. The primary endpoints were overall survival at 30 days and freedom from severe adverse events (SAE), which included myocardial infarction (MI), coronary artery re-operation, and re-thoracotomy, caused by bleeding and stroke. Results: The overall survival in both groups was 100% with no intraoperative OPCAB-to-on-pump conversion. The median procedure time was 169 min (interquartile range, 150-179 min) for Group 1 and 183 min (interquartile range, 169-205 min) for Group 2 (P<0.001). The overall freedom from SAE numbered 93.3% (98.3% vs. 88.3%, P=0.030). Postoperative MI rate was 2.5% (n=3) with no significant difference for either group (0 vs. 5.0%, P=0.100). One MI patient underwent a re-operation, and two other patients received a conservative treatment. A total of 2.5% (n=3) of patients underwent a re-thoracotomy on account of bleeding (0 vs. 5.0%, P=0.100); no anastomosis-related bleeding was detected. Blood transfusion was applied in 31.7% of patients (38.3% vs. 25.0%, P=0.090). A total of 1.7% of patients (1.7% vs. 1.7%, P=0.800) developed a stroke. Ventilation time, intensive care unit stay, and hospital stay were similar in both groups. Conclusions: ONCAB showed superior freedom from SAE and shorter procedure times when compared to OPCAB for multi-vessel coronary artery revascularization. 5640Zubarevich et al. On-pump versus off-pump for multi-vessel coronary revascularization