The aim of this study was to evaluate the capacity of the SYNTAX Score-II (SS-II) to predict long-term mortality in patients undergoing left main percutaneous coronary intervention (LM-PCI) treated with second-generation drug-eluting stents (DES). Data from 487 consecutive patients with de novo left main coronary artery disease undergoing PCI were retrospectively studied. The patients were divided into tertiles according to the SS-II: low SS-II tertile (SS-II 5 22), intermediate SS-I[ tertile (SS-II of 23 to 30), and high SS-II tertile (SS-II 30): The survival curves were estimated by the Kaplan Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the possible associations between the SS-I1 and the rates of long-term mortality. The predictive ability of the SS-I[ for mortality was assessed and compared with the SYNTAX score (SS) alone by an area under the receiver operator curve (AUC). The overall SS-II was 27.3 +/- 9.1. At a mean follow-up of 5.1 years, the long-term mortality was 6.0%. The rates of mortality were 2.4%, 3.4%, and 11.6%, respectively (P < 0.0001) in the low, intermediate, and high SS-II tertiles. The cardiac mortality rates were 1.8%, 1.4%, and 8.1%, respectively (P = 0.002) among patients in the 3 groups. By multivariate analysis, SS-II was an independent predictor of the long-term mortality (hazard ratio: 1.56, 95% confidence interval: 1.05 to 2.32; P = 0.03). The AUC demonstrated a substantially higher predictive accuracy of the SS-II for mortality compared with the SS alone (AUC was 0.689 and 0.596, respectively). In patients with LM-PCI treated with a second-generation DES, the SS-II is an independent predictor of long-term mortality and demonstrates a superior predictability compared with the SS alone.