Background: Sirolimus-eluting stent (SES; Cypher, Cordis Corp) and Paclitaxel-eluting stent (PES; TAXUS, Boston Scientifics) have shown to reduce effectively in-stent restenosis in various clinical trials. We investigated clinical and angiographical data of the patients in whom SES or PES was implanted and compared these two different drug-eluting stents. Methods: A multicenter cohort of consecutive patients treated with SES or PES during the period of April, 2003 ~ June, 2005 included 1297 patients with 1507 lesions. SES was implanted in 1038 lesions of 883 patients (61짹11 years, male 66.0%) and PES in 469 lesions of 414 patients (62짹10 years, male 30.5%). Clinical outcomes and angiographic follow-up data at 6 months were analyzed. Results: The baseline clinical characteristics showed no significant difference between the SES and PES groups. The baseline angiography showed a longer lesion length in SES group (SES 21.9짹9.1 mm vs. PES 19.5짹8.0 mm, <0.001), although there was no difference in the reference vessel diameter (RVD), minimal lumen diameter (MLD) and diameter stenosis (DS) between the two groups. The post-stenting angiographic data showed a slightly smaller MLD (SES 2.59짹0.69 mm vs. PES 2.80짹0.49 mm, p<0.001) and a longer total stent length (SES 30.4짹13.6 mm vs. 26.3짹11.1 mm, p<0.001) in SES group. The 6-month follow-up angiography which was performed in 661 lesion showed a smaller late loss (SES 0.24짹0.47 mm vs. PES 0.49짹0.72 mm, p<0.001) and a fewer in-segment restenosis rate (SES 4.6% vs. PES 11.5%, p<0.001) in SES group. There was a higher target lesion revascularization rate in PES than SES group (5.1% vs. 1.7%, p=0.006). However, other clinical events such as death (SES 1.4% vs PES 1.9%), myocardial infarction (MI; SES 0.7% vs. PES 1.5%) or subacute thrombosis (SAT; SES 1.1% vs. PES 1.9%) showed no statistical difference between the two groups. Conclusions: Based on the analysis of our multicenter registry data, SES was more effective to reduce in-stent restenosis and TLR than PES. However, the incidence of other clinical events such as death, MI or SAT was similar. Randomized multicenter trials are needed to validate this result.