There is uncertainty regarding the best revascularization approach-whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)-for obese patients suffering from multi-vessel coronary artery disease. 406 patients with low and intermediate SYNTAX scores (SS) underwent PCI with drug-eluting stents (n = 200, 100 with SS ≤ 22, and 100 with SS 23-32) and CABG (n = 206, 100 with SS ≤ 22, and 106 with SS 23-32). Patients were also categorized by body mass index (BMI): normal weight (12%, 48 patients), overweight (41.6%, 169 patients), and obese (46.6%, 189 patients). The follow-up period averaged 9 ± 1.9years. The endpoints of the study were as follows: major adverse cardiac and cerebrovascular events, a repeat revascularization, diminished left ventricular ejection fraction (LVEF), and high SS (≥ 33) observed over time. When comparing PCI and CABG in overweight individuals, the risk of myocardial infarction (MI) following PCI was greater than after CABG (Hazard Ratio [HR] 2.7, 95% Confidence Interval [CI] 1.1-6.7, p = 0.03). In patients with overweight and Class I obesity, CABG was associated with the risk of coronary atherosclerosis progression (SS ≥ 33) (HR 4.4, 95% CI 1.5-13, p = 0.009 and HR 4.9, 95% CI 1.9-12, p = 0.001, respectively); whereas PCI was connected with the likelihood of repeat revascularization (HR 2.7, 95% CI 1.6-4.55, p < 0.0001 and HR 2, 95% CI 1.3-3.1, p = 0.002,respectively). At the same time, for stented patients, Class III obesity was associated with the risk of repeat revascularization (HR 2.5, 95% CI 1.02-6, p = 0.044). There were no significant weight-related impacts on long-term outcomes among patients who underwent surgery. Whereas in stented patients, Class III obesity was associated with the risk of repeat revascularization. When comparing PCI and CABG, for overweight and Class I obesity patients, CABG was associated with a likelihood of coronary atherosclerosis progression (SS ≥ 33), while PCI was linked to the risk of repeat revascularization. For overweight patients, CABG outperformed PCI in terms of the risk of MI. For other adverse events in patients of different weight categories, PCI and CABG did not reveal any significant benefits.