Background: There is a renewed interest in combining clinical and angiographic information to predict risk of patients undergoing multivessel revascularization. The aim of this study was to investigate the ability to predict mortality of the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score, European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Global Risk Classification (GRC) in multi-vessel disease patients undergoing percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG). Methods and results: Between January 2003 and December 2005, the SYNTAX, EuroSCORE and GRC were assessed in patients with multivessel disease undergoing PCI with drug-eluting stent implantation (n=1547) or CABG (n=1495). Clinical outcomes in mortality and major cardiovascular events (MACE: composed of death, myocardial infarction, or stroke), were stratified according to tertiles of SYNTAX, EuroSCORE and GRC score. Results : During median 5.6 years follow-up, increasing levels of EuroSCORE had a trend toward a significantly higher rate of death, and significantly higher rates of MACE in PCI and CABG cohorts (all of P<0.001). Increasing levels of GRC score had a trend toward a significantly higher rate of death and MACE in PCI cohort (p<0.001) but not in CABG cohort (p=0.672 in death, p=0.413 in MACE). In both cohorts of PCI and CABG group, the SYNTAX score showed no statistically significant separation of the Kaplan Meier curves for death (p=0.051 in PCI cohort, p=0.273 in CABG cohort) and MACE (p=0.149 in PCI cohort, p=0.183 in CABG cohort). The respective C-statistics for the SYNTAX Score, EuroSCORE and GRC for mortality were 0.55, 0.66, and 0.59 in PCI cohort and 0.52, 0.67, and 0.57 in CABG cohort. Conclusion: In multivessel disease patients undergoing percutaneous or surgical revascularization, the EuroSCORE has the best prognostic accuracy compared with other stand–alone or combined score. The GRC has good predictive ability for PCI, but with the poor predictive ability for CABG.