Objective: To investigate the clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) in the treatment of patients with multivessel coronary artery disease. Methods: A total of 147 patients with multi-vessel coronary artery disease and coronary heart disease who underwent surgical treatment in Henan Provincial People's Hospital from March 2016 to March 2019 were retrospectively selected. Of which, 69 patients were treated by MICS CABG (minimally invasive group) and 78 patients were treated using the traditional thoracotomy (traditional group). The perioperative indexes, serum myocardial enzyme indexes and renal function indexes of patients before and after operation were compared between the two groups; Two groups of patients were followed up for 2 years; the incidence of adverse cardiovascular events (MACE) was recorded, and survival analysis was performed. Results: The age of the patients in the minimally invasive group and the traditional group were (66.9±5.8) and (68.2±7.0) years old, respectively, and the proportions of males were 60.9% (42 cases) and 51.3% (40 cases) (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the minimally invasive group were converted to thoracotomy. Before surgery, there was no significant difference in serum cTnI, CK-MB, BUN, Scr, and creatinine clearance between the minimally invasive group and the traditional group (all P>0.05). After re-examination 48 hours after operation, the serum cTnI in the minimally invasive group was (3.109±0.664) μg/L, and the CK-MB was (18.03±3.27) U/L, which were lower than those in the traditional group (3.438±0.715) μg/L, (20.63±4.28) U/L; the difference was statistically significant (all P<0.05). During the 2-year follow-up, there was no statiscally significant difference in the incidence of recurrent myocardial infarction, postoperative atrial fibrillation, postoperative stroke, arrhythmia, heart failure, thrombosis, cardiac death, and MACE events between the minimally invasive group and the traditional group. Statistical significance (all P>0.05). The survival curve analysis showed that the cumulative rates of MACE events in the minimally invasive and traditional groups were 17.39% and 26.92%, respectively (P=0.171). Conclusions: The effect of MICS CABG in the treatment of patients with multivessel coronary artery disease and coronary heart disease is not much different from that of traditional open thoracotomy, but the former is less traumatic, quicker after surgery, and has clinical significance for the recovery of patients' myocardial function.