Historically, coronary artery bypass graft (CABG) surgery has been the standard revascularization method for unprotected left main coronary artery (LMCA) disease. Over the last decade, several randomized controlled trials (RCTs) have shown favorable results for percutaneous coronary intervention (PCI) with drug-eluting stent (DES) compared with CABG; however, no RCT has been conducted directly comparing DESs with medical therapy alone (MTA). Furthermore, the 2 most recently reported larger RCTs, using new-generation DESs reached somewhat conflicting conclusions comparing the 2 revascularization strategies. Therefore, we performed a traditional pairwise meta-analysis and Bayesian network meta-analysis to compare the efficacies of the 3 currently available treatment strategies (MTA, CABG, and DES) for unprotected LMCA disease. Scientific databases and websites were searched to find RCTs. Data from 8 trials including 4,850 patients were analyzed. Overall PCI increased the risk of major adverse cardiac and cerebrovascular events (MACCEs) driven by increased rate of revascularization compared with CABG, but no differences in all-cause mortality, cardiac mortality, and recurrent myocardial infarction were found. However, early (i.e., within 30 days) PCI decreased the risk of MACCEs and stroke compared with CABG. In the mixed-treatment comparison models, both CABG and DESs were associated with better survival compared with MTA, but no difference was found between them. In conclusion, in patients with unprotected LMCA disease, PCI with DESs yields similar all-cause and cardiac mortalities compared with CABG. Furthermore, CABG increases early (i.e., within 30 days) MACCE rates, driven by an increased risk of stroke. Over longer durations, PCI increases MACCE rates because of increased recurrent revascularization.