Background: Multivessel or multilesion angioplasty is generally known to be associated with increased complexity of procedure and unfavorable prognosis. This study was to compare the mid-term clinical and angiographic outcomes of 3 or more Drug-eluting stent (DES) either Sirolimus-eluting stent (SES; Cypher^TM) or Paclitaxel-eluting stent (PES; Taxus^TM) implantation to those of single DES implantation. Methods: A total 42 patients (pts) with 105 lesions were implanted with 3 or more DESs (3 SES in 30 pts, 4 in 8 pts, 5 in 2 pts, 7 in 1 pt and 10 in 1 pt; the Multiple DES group) and 184 pts with 205 lesions with single DES (the Single DES group) in a variety of coronary lesions. Standard anticoagulation with heparin was maintained during the procedure. The in-hospital and 6-month clinical outcomes and 6-month angiographic outcomes of both groups were compared. Results: Baseline characteristics were similar between the two groups except history of DM (10.5% vs. 4.5%, P=0.03) which was higher in the Single DES group. Total 247 lesions were treated with 133 Cypher, 108 Taxus and 6 Hybrid (both Cypher and Taxus). The Multiple DES group had higher incidence of periprocedural CK-MB elevation, numerically longer hospital and ICU stay. At 6 months, clinical outcomes including death, Q-wave MI, TLR and TVR were not different between two groups however, mean restenosis lesion length was longer in multiple DES group (Table). Conclusions: Treatment of multivessel or multilesion with 3 or more DES is associated with increased periprocedural complications and diffuse in-stent restenosis but showed similar clinical outcomes up to 6 months compared with single DES. These findings suggest that special caution should be exercised when DES used for multivessel disease.