ObjectiveTo summarize the application experience of off-pump total arterial coronary artery bypass grafting with left internal thoracic artery and bilateral radial arteries, and evaluate its safety and efficacy. MethodsThe clinical data of the patients with severe multiple coronary arteries stenosis undergoing off-pump total arterial coronary artery bypass grafting with left internal thoracic artery and bilateral radial arteries in the Affiliated Hospital of University of Electronic Science and Technology ＆ Sichuan Provincial People’s Hospital from November 2020 to April 2023 were retrospectively analyzed. Results Finally 24 patients were enrolled. There were 23 males and 1 female. The mean age was 53.63±4.33 years. The cardiac function class was from grade Ⅱ to Ⅲ according to New York Heart Association. There were 3.17±0.38 distal anastomoses. Y graft in 12 patients and sequential graft in 4 patients were performed. Coronary endarterectomy in 1 patient, intraaortic balloon pump (IABP) catheter implantation in 10 patients, and thymoma resection in 1 patient were also performed simultaneously. The operation time was 308.13±30.39 mi. The ventilator support time was 15.42±7.42 h, and the intensive care unit stay time was 46.08±27.32 h. The postoperative hospital stay time was 11.71±1.90 d. There were no death, but acute renal failure in 1 patient and cerebral infarction in 1 patient were found after operation. The postoperative left ventricular end diastolic diameter by echocardiogram before discharge was significantly reduced, the postoperative left ventricular ejection fraction and short axis shortening rate were significantly increased, compared to preoperative ones (P≤0.05). All arterial grafts were patent suggested through coronary artery computed tomography angiography (CTA) examination before discharge. All patients were followed up for 14.58±8.75 months. No angina recurrence and death were found. All arterial grafts were still patent in 16 patients suggested through coronary artery CTA or angiography examination at 1 year after operation. Conclusion Off-pump total artery coronary artery bypass grafting with left internal thoracic artery and bilateral radial arteries for patient with severe multiple coronary arteries stenosis is safe and effective. For high-risk patient, IABP assistance during operation is recommended.