Abstract Aims Clinical outcomes according to the status of renal insufficiency were not fully evaluated in patients with significant left main coronary artery disease (LMCAD). Methods and results The current study analyzed 4894 patients with unprotected LMCAD enrolled in the multicenter IRIS-MAIN registry. Renal insufficiency was graded according to the baseline renal function (eGFR). The primary clinical outcome was major adverse cardiocerebrovascular event (MACCE), defined as a composite of death, myocardial infarction, stroke, and any revascularization. At baseline, 3824 (78%) had preserved renal function (eGFR ≥60 ml min–1 1.73m–2), 838 (17%) had moderate renal dysfunction (eGFR of ≥30 and <60), and 232 (5%) had severe renal dysfunction (eGFR <30). At 2 years, the rates of MACCE were significantly higher in patients with lower levels of eGRF (9.1% in eGRF ≥60, 16.0% in eGFR of ≥30 and <60, and 36.2% in eGRF <30, respectively, P<0.001). After multivariable adjustment, as compared with patients with eGFR ≥60, the hazard ratios (HR) for MACCE proportionally increased for patients with eGFR of ≥30 and <60 (HR 1.46, 95% CI 1.18–1.79) and for those with eGFR <30 (HR 3.39, 95% CI 2.61–4.40). The adjusted risks for MACCE was similar between percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG) in patients with preserved and moderate renal dysfunction. However, in patients with severe renal dysfunction, PCI was associated with a significantly higher risk of MACCE compared to CABG (38.5% vs. 24.7%, HR 1.80, 95% CI 1.03–3.13, P=0.04). Crude and Adjusted Risk of Primary Composite Outcome After PCI and CABG, According to the Status of Baseline Renal Function Patient Groups 2-Year Event Rate, n (%) Crude Risk Adjusted Risk* Revascularization type HR 95% CI P value HR 95% CI P value PCI CABG (reference) All patients 306/2825 (10.8) 144/1453 (9.9) 1.160 0.952–1.414 0.141 1.265 1.036–1.546 0.021 Subgroups by baseline eGFR Preserved renal function (eGFR >60) 190/2289 (8.3) 89/1098 (8.1) 1.080 0.840–1.389 0.549 1.125 0.874–1.449 0.360 Moderate renal dysfunction (eGFR ≥30 and <60) 71/419 (169%) 37/282 (13.1%) 1.394 0.936–2.074 0.102 1.276 0.854–1.909 0.234 Severe renal dysfunction (eGFR <30) 45/117 (38.5%) 18/73 (24.7%) 1.997 1.154–3.458 0.014 1.798 1.032–3.130 0.038 Conclusions The degree of renal insufficiency was proportionately associated with worse clinical outcomes in patients with LMCAD. In patients with severe renal dysfunction of eGFR of <30, PCI was associated with a higher risk of MACCE as compared with CABG. Acknowledgement/Funding This work was supported by a grant from the CardioVascular Research Foundation, Seoul, Korea (2015-09).