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Background: As surgical techniques continue to evolve, the optimal approach for revascularizing multi-vessel coronary artery disease (CAD) remains a matter of ongoing debate. Accordingly, our objective was to compare and contrast various surgical techniques utilized in the management of multi-vessel CAD. Methods: A systematic literature review was performed using PubMed, Embase, and Cochrane central register of controlled trials from inception to May 2022. Random-effects network meta-analysis was performed for the primary outcome; target vessel revascularization (TVR), and secondary outcomes; mortality, major adverse cardiac and cerebrovascular events, postoperative myocardial infarction, new-onset atrial fibrillation, stroke, new-onset dialysis, in patients undergoing percutaneous coronary intervention (PCI) with a stent, off-pump coronary bypass graft, on-pump coronary artery bypass graft (ONCABG), hybrid coronary revascularization, minimally-invasive coronary artery bypass, or robot-assisted coronary artery bypass (RCAB) surgeries. Results: A total of 8841 patients were included from 23 studies. The analysis showed that ONCABG had the highest freedom from TVR, with a mean (SD) absolute risk of 0.027 (0.029); although ONCABG was found to be superior to all other methods, it was only significantly better than first-generation stent PCI. While RCAB did not demonstrate significant superiority over other treatments, it showed a greater probability of preventing postoperative complications. Notably, no significant heterogeneity was calculated for any of the reported outcomes. Conclusions: ONCABG shows a better rank probability compared to all other techniques for preventing TVR, while RCAB offers greater freedom from most postoperative complications. However, given the absence of randomized controlled trials, these results should be interpreted with caution. [ABSTRACT FROM AUTHOR]