Background The Syntax score was recently developed as a comprehensive, angiographic tool grading the complexity of coronary artery disease (CAD). It aims to assist in patient selection and risk stratification of patients with extensive CAD undergoing revascularization. However, the prognostic value of the Syntax score in patients undergoing percutaneous coronary intervention (PCl) has not been validated. The aim of this study was to evaluate its role in predicting long-term incidences of major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing PCl for 3-vessel disease.Methods Two hundred and three consecutive patients with de novo 3-vessel CAD undergoing PCI with sirolimus-eluting stents were studied. Their angiograms were scored according to the Syntax score. The patients were divided into tertiles according to the Syntax score: lowest Syntax score tertile (Syntax score ≤22), intermediate Syntax score tertile (Syntax score of 23 to 32), and the highest Syntax score tertile (Syntax score ≥33). During the 1-year follow-up, the MACCE-free survival curves were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the Syntax score and the incidence of MACCE. Performance of the Syntax score was studied with respect to predicting the rate of MACCE by receiver operator characteristic (ROC) curves with an area under the curve.Results The overall Syntax score ranged from 6 to 66 with mean ± standard deviation of 27.9±12.6 and a median of 26.At 1 year, the Syntax score significantly predicted the risk of MACCE (HR 1.07/U increase, 95% Cl 1.04 to 1.11, P＜0.001). The rate of MACCE was significantly increased among patients in the highest Syntax score tertile (17.9%) as compared with those with the lowest Syntax score tertile (1.4%, P ＜0.001) or intermediate Syntax score tertile (6.2%,P=0.041). After the adjustment for all potential confounders, the Syntax score remained a significant predictor of the rate of MACCE (adjusted HR 1.12/U increase, 95% Cl 1.05 to 1.20, P ＜0.001). The Syntax score accurately predicted MACCE with an area under the receiver operator curve of 0.77 (95% Cl 0.65 to 0.90, P ＜0.001). A Syntax score of 29.5was identified as the optimal cutoff to predict MACCE with a sensitivity of 82.4% and specificity of 65.6%.Conclusion The Syntax score predicts the risk of MACCE in patients with 3-vessel disease undergoing PCl.