Objective: The clinical outcomes for unprotected left main coronary artery (LMCA) between coronary artery bypass grafting (CABG) and drug-eluting stents (DES) are still controversial. The objective was to compare safety and efficacy between DES and CABG for unprotected LMCA. Methods: Electronic databases and article references were systematically searched (2000–2010) to access relevant studies. Results: Fifteen studies with 5,479 patients were finally involved in the present study. The mortality was similar in DES and CABG groups at 1 year [odds ratio (95% confidence interval): 0.71 (0.5–1.03)], 2 years [1.28 (0.93–1.76)], 3 years [0.88 (0.53–1.46)], 4 years [0.46 (0.18–1.17)], and 5 years [1.16 (0.85–1.57)]. No significant difference was found between DES and CABG in the risk of composite endpoint of death, myocardial infarction and cerebrovascular events during 5 years’ follow-up [1 year, 0.95 (0.63–1.43); 2 years, 1.34 (0.67–2.57); 3 years, 1.06 (0.59–1.90); 4 years, 0.53 (0.26–1.08); 5 years, 0.83 (0.33–2.07)]. However, the risk of repeat revascularization was significantly higher in the DES group than the CABG group at 1 year [5.00 (2.85–8.77)], 2 years [4.79 (2.72–8.45)], 3 years [5.72 (3.07–10.65)], 4 years [2.16 (1.17–4.01)], and 5 years [5.65 (3.44–9.27)]. Conclusion: Our meta-analysis indicates that there are no significant differences in the safety between CABG and DES in patients with unprotected LMCA in the 5 years after intervention. But CABG is superior to DES for repeat revascularization.