We sought to assess real-world implementation of the guidelines in patients with multivessel coronary artery disease (CAD) using a prospective national registry in Israel.All consecutive patients with left main or 2- to 3-vessel CAD involving the proximal or mid left anterior descending artery were enrolled in a dedicated multicenter registry. Patients were managed at the discretion of the treating team at each hospital and were followed for 30 months.This registry included 1,064 patients, 55% treated with percutaneous coronary intervention (PCI) and 45% with coronary artery bypass surgery (CABG). Multivariate logistic regression analysis showed that chronic renal failure (odds ratio [OR], 2.43; p = 0.001) and prior myocardial infarction (OR, 1.7; p = 0.024) were associated with referral to PCI versus CABG, whereas male gender (OR, 2.27; p < 0.001), prior aspirin treatment (OR, 1.72; p = 0.005), diabetes mellitus (OR, 1.51; p = 0.007), 3-vessel CAD (OR, 3.45; p < 0.001) and SYNTAX score (SS) greater than 32 (OR, 10.0; p < 0.001) were associated with referral to CABG versus PCI. Each point increment in the SS was independently associated with a 9% greater likelihood of referral to CABG (p < 0.001). Survival analysis showed that mortality risk was lower among PCI patients less than 8 months after the procedure, and CABG was associated with a significant survival benefit thereafter.We found good agreement with current guidelines regarding revascularization strategies in real-world patients with multivessel CAD. The SS was the main independent predictor associated with the choice of revascularization strategy. The time-dependent association between revascularization strategy and long-term survival should be incorporated in the risk assessment of this population.