Hybrid coronary revascularization (HCR) involves the use of minimally invasive direct coronary artery bypass grafting (CABG) to treat the left anterior descending artery (LAD), and percutaneous coronary intervention to treat non-LAD vessels. We reported the results of a comparative analysis between HCR and off-pump CABG via sternotomy (OPCABG). Data were retrospectively collated from patients who underwent HCR or OPCABG for multivessel coronary artery disease between 2011 and 2022. Propensity score-based matching was performed to reduce the selection bias. The Comparisons of cardiac-related death, major adverse cardiac and cerebrovascular events (MACCE), and repeat revascularization were performed by Kaplan-Meier analysis or the Fine-Gray test. After matching, the baseline characteristics were well-balanced between the two groups with 91 patients per group. There was no significant difference in operative mortality rate (1.1% for HCR vs2.2% for OPCABG, p = 1.000). However, patients undergoing HCR required a significantly lower rate of blood product transfusions (p < .001) and experienced significantly fewer pulmonary complications than OPCABG patients (p < .001). At 10 years, the incidences of cardiac-related death, MACCE and repeat revascularization did not differ significantly between the two groups (9.5% vs11.5%, p = .277; 4.7% vs12.3%, p = .361; 1.2% vs2.5%, p = .914, respectively). For patients with multi-vessel lesions, HCR was comparable to OPCABG in long-term outcomes such as cardiac-related death, MACCE, and the durability of grafts. Additionally, HCR was better than OPCABG in perioperative outcomes. HCR may be an alternative therapy for OPCABG in patients with multi-vessel coronary artery disease.