Ostial coronary artery lesions can be challenging during percutaneous coronary intervention (PCI) because of elastic fiber content, calcium burden, and angulation. We assessed procedural and clinical major adverse cardiac events (MACE) associated with PCI for ostial lesions, focusing on ostial left circumflex (LC) lesions compared with ostial left anterior descending artery (LAD) and right coronary artery lesions. All patients with ostial or very proximal coronary artery lesions treated with PCI at MedStar Washington Hospital Center (Washington, DC) from 2003 to 2018 were included. The primary end point was target lesion revascularization (TLR)-MACE, defined as the composite of all-cause mortality, Q-wave myocardial infarction (MI), and TLR at 1 year. A total of 4,759 patients with available 1-year follow-up were included: 2,236 ostial/very proximal LAD, 980 ostial/very proximal LC, and 1,543 ostial/very proximal right. The presenting clinical syndrome for the LC group was mainly stable or unstable angina, whereas MI was more common in the LAD. At 1 year, the TLR-MACE rate was 16.7% in the LC group versus 12.5% in the LAD and 11.8% in the right group (p = 0.001). Mortality rates were 11.2% in the LC group versus 8.4% in the LAD and 6% in the right group (p <0.001). A Cox model showed that dialysis had the highest impact on TLR-MACE. In conclusion, compared with PCI of ostial or very proximal LAD or right lesions, PCI of ostial or very proximal LC lesions was associated with higher rates of TLR-MACE.