Background: For the treatment of unprotected left main coronary artery (ULMCA) disease, although coronary artery bypass grafting (CABG) is recommended by the current practice guidelines, percutanous coronary intervention (PCI) with drug-eluting stents (DES) has recently emerged as an alternative to CABG. However, there are limited data regarding whether the newer generation DESs is associated with better outcomes as compared with first generation DESs in treating ULMCA disease. Methods: A total 162 patients (pts) who underwent PCI with DESs for ULMCA were enrolled for current study. We compared angiographic and clinical outcomes of first generation DESs [Paclitaxel-eluting stents (Taxus���) and Sirolimus-eluting stents (Cypher���)] versus newer generations DESs [Zotarolimus-eluting stents (Endeavor Resolute���) and Everolimus-eluting stents(Promus Element��� and Xience���). Results: Baseline characteristics were similar between the two groups except that newer generations DESs group had a higher male gender (84.2% vs.65%, p=0.025). At index procedure, there was trend towards higher use of IVUS in newer generations DESs group (64.9% vs. 47.6%, p=0.065) whereas more use of final kissing balloon in first generation DESs group (44.4% vs. 28.9%, p=0.091). However, at six months, there were no differences in major angiographic outcomes and similar results were found in major clinical outcomes up to twelve months. Interestingly, the DES associated aneurysms were found only after the first generation DESs implantation (Table). Conclusions: In the current study, there were no significant differences between first & newer generations DESs at 6 months angiographic and 12 months clinical outcomes following ULMCA intervention.