Previous meta-analyses showed that drug-eluting stent (DES) implantation may serve as an alternative to coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) stenosis, largely driven by data from registries. Hence, we performed a meta-analysis of randomized controlled trials (RCTs) to overcome this limitation. PubMed, the Cochrane Library, and Scopus were systematically searched through October 2016 to identify eligible RCTs. The primary outcomes were major adverse cardiac and cerebrovascular events (MACCE) at 1-year and long-term (≥3 years) follow-ups. This meta-analysis included 5 RCTs, totaling 4,595 patients with ULMCA disease. Compared with CABG, DES showed similar 1-year rates of MACCE (risk ratio [RR] 1.14, 95% confidence interval [CI] 0.91–1.42), all-cause death, and myocardial infarction, with a higher incidence of revascularization (RR 1.68, 95% CI 1.24–2.27) and lower incidence of stoke (RR 0.43, 95% CI 0.23–0.78). At long-term follow-up, DES placement was inferior to CABG in terms of MACCE (RR 1.27, 95% CI 1.13–1.43) and revascularization (RR 1.70, 95% CI 1.43–2.01). There was no difference in long-term risk of other outcomes between these 2 strategies. In conclusion, DES stenting and CABG for ULMCA disease yield comparable rates of MACCE at 1-year follow-up; however, CABG is associated with a decreased risk of long-term MACCE compared with DES, exclusively driven by the considerable reduction in revascularization events.