Background Whether SYNTAX score should be used as a stand-alone tool or whether its performance may be improved by the parallel use of clinical scores focusing on comorbidities, such as EuroSCORE, is a matter of debate. Methods A combined risk model including both clinical and angiographic information was developed, and its performance tested on a contemporary population of 255 patients with left main disease undergoing percutaneous coronary intervention (PCI). A global risk classification (GRC) system was created by combination of SYNTAX score and EuroSCORE strata, and new classes of risk were defined. Results When EuroSCORE was fitted into the SYNTAX score model, c-statistic increased from 0.681 to 0.732 for the prediction of cardiac mortality. The likelihood ratio test for the significance of adding the EuroSCORE term to the model was χ2 = 4.109 ( P = .043) with a net reclassification improvement of 26% ( P = .002). GRC showed the best prediction and discriminative ability in terms of two-year cardiac mortality (HR 3.40, 95% CI 1.79-6.43, P < .001; c-statistic 0.756) as compared with SYNTAX score (HR 2.87, 95% CI 1.35-6.10, P = .006; c-statistic 0.747) and EuroSCORE (HR 3.04, 95% CI 1.41-6.57, P = .005; c-statistic 0.708) alone. Conclusions We found a significant improvement in the prediction of cardiac mortality with the inclusion of EuroSCORE in a SYNTAX score-based model. The degree of reclassification between treatment threshold categories indicates that clinical and angiographic information are both important for assessing individual risk of patients undergoing left main PCI.