Background: Influence of two-stent strategy on long-term clinical outcome, compared with single-stent, in drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) bifurcation stenosis has not been evaluated in detail. Methods: This study included 217 patients with de novo coronary lesions at the ULMCA bifurcation who were electively treated with DES. The patients were treated with single stent placement in the main vessel alone (124 patients) or two stent placement in both branches (93 patients). Cox proportional hazard regression analyses were performed to correct for independent predictors of adverse outcomes between the two groups. Results: Sirolimus- and paclitaxel-eluting stent was used in 96% and 4%, respectively. The two-stent strategy comprised of crush technique (21%), kissing stenting (18%), and T stenting (5%). The two-stent group was more unstable, had more involvement of three vessel stenosis and right coronary artery, and was treated with more use of glycoprotein IIb/IIIa inhibitor and DESs. The follow-up period was 861짹324 days in the two-stent and 918짹289 in the single-stent (p=0.175). Two-year outcomes with adjusted hazard ratios are presented in the table. Conclusions: For ULMCA bifurcation stenoses, the two-stent strategy was independently associated with the increase of major adverse cardiac events, driven by higher target lesion revascularization (TLR) rate compared with single-stent technique.