Background Although intravascular ultrasound (IVUS)-guidance has been found useful in stenting for unprotected left main coronary artery (LMCA) stenosis, its impact on long-term mortality is still unclear. We therefore compared long-term outcomes of IVUS-guided and conventional angiography-guided stenting for unprotected LMCA stenosis. Methods and Results In the MAIN-COMPARE registry, patients with unprotected LMCA stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the two groups were compared using the propensity-score matching in the entire and separate populations according to the stent type. In 201 matched pairs of overall population, there was a tendency of lower risk of 3-year morality with IVUS-guidance compared with angiography-guidance (6.0% vs. 13.6%, p=0.063; hazard ratio [HR], 0.54, 95% confidence interval [CI], 0.28-1.03). In particular, in 142 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was significantly lower with IVUS-guidance as compared with angiography-guidance (4.7% vs. 16.0%, p=0.048; HR, 0.39; 95% CI, 0.15-1.02). In contrast, the use of IVUS-guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% vs. 10.8%, p=0.346; HR, 0.59; 95% CI, 0.18-1.91). The risk of myocardial infarction or target vessel revascularization was not associated with use of IVUS-guidance. Conclusions Elective stenting with IVUS-guidance, especially in the placement of drug-eluting stent, may reduce long-term mortality rate for unprotected LMCA stenosis when compared with conventional angiography-guidance