OBJECTIVES This study evaluated the clinical outcomes of consecutive, selected patients treated with coronary artery bypass graft (CABG) Surgery or percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main coronary artery (ULMCA) disease. BACKGROUND Although recent data suggest that PCI with DES provides better clinical outcomes compared to bare-metal stenting for ULMCA disease, there is a paucity of data comparing PCI with DES to CABG. METHODS Since April 2003, when DES first became available at our institution, 123 patients underwent CABG, and 50 patients underwent PCI with DES for ULMCA disease. RESULTS High-risk patients (Parsonnet score > 15) comprised 46% of the CABG group and 64% of the PCI group (p = 0.04). The 30-day major adverse cardiac and cerebrovascular event (MACCE) rate for CABG and PCI was 17% and 2% (p < 0.01), respectively. The Mean follow-up was 6.7 +/- 6.2 months in the CABG group and 5.6 +/- 3.9 months in the PCI group (p = 0.26). The estimated MACCE-free survival at six months and one year was 83% and 75% in the CABG group versus 89%and 83% in the PCI group (p = 0.20). By multivariable Cox regression, Parsonnet score, diabetes, and CABG were independent predictors of MACCE. CONCLUSIONS Despite a higher percentage of high-risk patients, PCI with DES for ULMCA disease was not associated with an increase in immediate or medium-term complications compared with CABG. Our data Suggest that a randomized comparison between the two revascularization strategies for ULMCA may be warranted.