This study compared the long term outcomes in patients with unprotected left main coronary artery (LMCA) disease who underwent stenting under the guidance of intravascular ultrasound (IVUS) or conventional angiography at a large single center. The primary outcome was the composite of all-cause death and myocardial infarction (MI) at 3 years. Target vessel revascularization (TVR) at 3 years was one of the secondary outcomes. Between January 2004 and December 2011, a total of 1,899 patients who underwent IVUS-guided (n = 713, 37.5%) or conventional angiography-guided (n = 1186, 62.5%) stenting were included. At 3 years, the unadjusted primary outcome trended lower in the IVUS-guided group versus the angiography-guided (6.9% vs. 8.4%, p = 0.22) although the TVR was similar between two groups (6.0% vs. 6.0%, p = 0.97). However, after adjustment for differences in baseline risk factors, IVUS-guidance was associated with significantly lower incidence of the composite of all-cause death and MI (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.50 to 0.84; p = 0.001), although there was still no significant difference in TVR between the two groups (HR: 1.09; 95% CI: 0.84 to 1.42; p = 0.53). IVUS guidance has benefits in improving the long-term prognosis for unprotected LMCA stenting.