Previous studies reporting long-term (≥5 year) clinical outcome in patients with unprotected left main coronary artery (LMCA) disease undergoing drug-eluting stent (DES) implantation are currently limited, although late adverse events beyond 1 year are one of the major concerns of DES. We evaluated long-term clinical outcomes in 134 consecutive patients who underwent sirolimus-eluting stents (SES) for unprotected LMCA lesion in a single center from 2004 to 2009. The median follow-up duration was 3.8 (range: 0.5–7.9) years. Eight patients suffered from serious cardiovascular events potentially related to LMCA lesion (primary outcome measure) (sudden cardiac death: N = 5, emergent coronary revascularization for the LMCA lesion: N = 2, and acute congestive heart failure related to LMCA lesion: N = 1) with the cumulative 5-year incidence of only 4.4 %. The cumulative 5-year incidence of all-cause death, cardiac death, target vessel myocardial infarction, definite stent thrombosis, and target-lesion revascularization was 26.5, 8.1, 0, 0, and 12.9 %, respectively. In a subgroup analysis, the cumulative incidence of the primary outcome measure was significantly higher in patients with 2-stenting (N = 27) than in patients with 1-stenting (N = 107) (14.0 and 2.2 %, P < 0.001). All 8 patients with serious adverse events had a true bifurcation lesion and 5 patients received 2-stenting for the LMCA lesion. SES implantation in patients with unprotected LMCA lesion was associated with a favorable long-term outcome with acceptably low rate of serious adverse event potentially related to LMCA lesion. However, complex LMCA lesions necessitating 2-stenting strategy might be associated with higher risk for serious adverse events.