Background: The two main first generation drug-eluting stents (DES); Sirolimus- (SES; Cypher) and Paclitaxel (PES; Taxus) eluting stent is effective in reducing intimal hyperplasia but recently safety issues related to profound delayed healing and associated stent thrombosis was suggested. We compared the safety and efficacy of those two first generation DESs implanted in unprotected left main (LM) artery up to 12 months. Methods: All patients (pts) with unprotected LM lesion electively treated either with SES or PES was enrolled. LM bifurcation lesions were treated by kissing stenting, crushing technique or stent crossover (Stent/Balloon). All pts received aspirin, clopidogrel (300-600 mg) and/or cilostazol as the antiplatelet regimen and unfractionated heparin was given during the PCI. Clinical and angiographic outcomes up to 12 months were investigated. Results: Out of total 136 pts who underwent percutaneous coronary intervention (PCI) on unprotected LM lesion, 76 pts (76/136, 55.8%) were exclusively treated with SES and 38 pts (38/136, 27.9%) with PES. Six-month angiographic outcomes were similar between the two groups. However, the cumulative incidence of stent thrombosis up to 1 year was higher in the PES group which has translated into a trend toward higher incidence of Q-wave myocardial infarction (MI). Other major clinical outcomes including mortality, repeat PCI and overall major adverse cardiac events (MACEs) were similar between the two groups at least up to 12 months (Table). Conclusion: Midterm angiographic outcomes and cumulative clinical outcomes were favorable and similar between the SESs and PESs up to 12 months except higher incidence of stent thrombosis in the PES group which has translated into a higher chance of Q-wave MI.