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Background: The optimal treatment of unprotected left main (UPLM) with either PCI or CABG remains uncertain., Aim: The purpose of this study was to determine the comparative safety and efficacy of PCI versus CABG in patients with UPLM disease., Methods: Search of BioMedCentral, CENTRAL, mRCT, PubMed, major cardiological congresses proceedings and references cross-check (updated November 2016). Outcomes were the rate of MACE [all cause death, MI, stroke], the rates of the individual components of MACE and the rate of target vessel revascularisation (TVR)., Results: We identified 6 Randomised Controlled Trials totalling 4717 patients allocated to PCI or CABG. At 1 year follow up, PCI and CABG were substantially equivalent with respect to the rates of MACE [PCI 8.5% vs CABG 8.9%, OR 1.02,(0.76-1.36), p = 0.9], death [PCI 5.4% vs CABG 6.6%, OR 0.81,(0.63-1.03),p = 0.08] and MI [PCI 3.4% vs CABG 4.3%, OR 0.80(0.59-1.07), p = 0.14]. Notably, PCI was associated with a significantly lower rate of stroke [PCI 0.6% vs CABG 1.8%, OR 0.36,(0.17-0.79), p = 0.01] and with a significantly higher rate of TVR [PCI 8.7% vs CABG 4.5%, OR 2.00(1.46-2.75), p<0.01]. At a median follow up of 5years, the rates of MACE were similar between the two strategies: PCI 14.6% vs CABG 13.8%, OR 1.02(0.76-1.38), p = 0.89. Likewise, the rates of death [PCI 8% and CABG 7.7%, OR 1(0.77-1.31), P = 0.9], MI [PCI 6.1% vs CABG 5%, OR 1.41(0.85-2.34), P = 0.19, I2 59%], and stroke [PCI 2% vs CABG 2.2%, OR 0.85(0.42-1.81), p = 0.65,] were similar while PCI was associated with a significantly higher rate of TVR [14.5% vs CABG 8.9%, OR 1.73(1.41-2.13), p<0.01]., Conclusion: In patients with UPLM disease, PCI and CABG are associated with similar rates of MACE and mortality at 1 year as well as after 5 years. Differences can be detected for individual end points at both short and long term FU.