Multivessel coronary artery disease (MVCD), defined as the presence of ≥50% diameter stenoses in two or more major coronary epicardial arteries, is frequently encountered in patients with both acute and chronic coronary syndrome. Optimal medical therapy and myocardial revascularization are the standards of care for the improvement of prognosis and quality of life in patients with MVCD. Nowadays, myocardial revascularization in the setting of MVCD can be successfully achieved by either percutaneous coronary intervention or coronary artery bypass grafting. The clinical outcomes of these two revascularization strategies have been compared across several randomized clinical trials and real-life registries. Data from these studies have demonstrated that a wide array of clinical and procedural factors contribute to determine the prognosis of MVCD patients. Considering all these aspects, stratifying the early and long-term risk of adverse events is crucial for establishing an optimal treatment strategy. Risk scores that incorporate and weight the prognostic relevance of different anatomical and clinical characteristics have been developed. Information conveyed by risk scores is useful to inform clinical decision-making in this complex clinical scenario.