OBJECTIVES: The impact of simultaneous coronary artery bypass grafting (CABG) with cerebral revascularization versus CABG alone on perioperative complications and short-term outcomes remains controversial in patients with simultaneous coronary and cerebrovascular disease. Our study was specifically designed to evaluate the effects of simultaneous cardio-cerebrovascular revascularization versus isolated off-pump CABG (OPCABG) in patients with severe carotid stenosis. METHODS: This retrospective analysis included patients undergoing OPCABG between May 2023 and May 2025. Participants were divided into two groups based on simultaneous carotid revascularization status, including the combined cardio-cerebrovascular revascularization group (n = 57) and the isolated OPCABG control group (n = 60). The primary endpoints comprised 30-day mortality and all-cause mortality during follow-up. Cardiac, hepatic, and renal function biomarkers were monitored daily for three consecutive postoperative days. Kaplan-Meier analysis demonstrated the survival probability of patients undergoing different surgical procedures throughout the follow-up period. RESULTS: Our study with a median follow-up of 11.5 months (IQR: 6.8-20.0 months) observed a lower short-term mortality rate of 5.3% (3/57) in the combined cardio-cerebrovascular revascularization group. Our results demonstrated no significant differences in 30-day mortality and all-cause mortality during follow-up between the combined cardio-cerebrovascular intervention and isolated OPCABG. No intergroup differences were observed in cardiac, hepatic, or renal function within the first three postoperative days. The combined surgical approach reduced hospitalization duration. CONCLUSION: Our findings demonstrated comparable short-term outcomes between patients receiving simultaneous cardio-cerebrovascular revascularization and those undergoing isolated CABG. This simultaneous intervention represents a clinically meaningful advancement in managing systemic vasculopathy.