Coronary artery bypass grafting (CABG) is the preferred revascularization strategy for unprotected left main disease (UPLMD). Multiple small-scale trials and registry data showed that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is a noninferior strategy with a Class IIa American College of Cardiology/American Heart Association recommendation in patients with high surgical risk and favorable anatomy. However, 2 recent large-scale randomized trials showed conflicting evidence. We conducted a meta-analysis of the existing data to compare outcomes of PCI with DES versus CABG for UPLMD. Four randomized and 8 nonrandomized trials involving 10,284 patients were included. Primary end point was composite of death, stroke, or myocardial infarction (MI) at 3 years or longer. Secondary end points were MACCE (Major Adverse Cardiac and Cerebrovascular Events) and its individual components (death, stroke, MI, or repeat revascularization). Mantel-Haenszel random effects model was used to calculate combined odds ratio for outcomes. A separate analysis of randomized data was also performed. There was no significant difference in primary composite outcome between PCI and CABG. However, MACCE was significantly higher in PCI, primarily driven by significantly high repeat revascularization. A subgroup analysis stratified by Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score showed that MACCE and repeat revascularization were not significantly different between PCI and CABG in low to intermediate SYNTAX score (<33), whereas they were significantly higher in PCI with higher SYNTAX score. Thus, although CABG remains the preferred method of treatment in UPLMD, PCI with DES can be considered as a reasonable alternative in patients with favorable anatomy and high surgical risk.