Despite the usefulness of intravascular ultrasound (IVUS) in percutaneous coronary intervention (PCI), the impact of IVUS guidance on clinical outcomes, particularly for chronic total occlusion (CTO) intervention, has rarely been studied. We sought to investigate the clinical usefulness of IVUS-guided CTO intervention with second-generation drug-eluting stent implantation. From 2007 to 2009, a total of 2,568 patients were enrolled in the Korean-CTO registry and 534 patients with successful implantation of second-generation drug-eluting stents were analyzed. IVUS-guided PCI was performed on 206 patients (39%). Clinical outcomes at 2 years were compared between the IVUS-guidance group and the angiography-guidance group in 201 propensity score-matched pairs. The primary end point was the occurrence of definite or probable stent thrombosis. Clinical characteristics were similar between both groups after matching. At 2 years, the IVUS-guidance group showed significantly less stent thrombosis than the angiography-guidance group (0% vs 3.0%, p = 0.014) and a lesser trend toward myocardial infarction (1.0% vs 4.0%, p = 0.058). Target lesion revascularization (TLR) and major adverse cardiovascular event rates were similar. However, a significant interaction was observed between the use of IVUS and lesion length for predicting the TLR (p = 0.037), suggesting usefulness of IVUS in long-lesion (≥3 cm) relative to short-lesion CTO. In conclusion, although IVUS-guided CTO PCI was not associated with a reduction in overall major adverse cardiovascular events, IVUS guidance appears to be associated with a reduction of stent thrombosis and myocardial infarction compared with angiography-guided CTO PCI. Additionally, TLR occurred less frequently in the IVUS-guidance group, especially for long lesions.