BackgroundPercutaneous coronary intervention (PCI) of left main (LM) chronic total occlusions (CTO) has received limited study.MethodsWe compared the clinical and procedural characteristics and outcomes of patients who underwent LM versus non‐LM CTO PCI at 41 US and non‐US centers between 2012 and 2024.ResultsDuring the study period 85 of 15,254 CTO PCIs (0.6%) performed in 14,969 patients were LM CTO PCIs. LM CTO PCI patients were older, had higher rates of dyslipidemia and heart failure and most (88.8%) had prior coronary artery bypass graft surgery (CABG). They were more likely to have moderately or severely calcified lesions (80.7% vs. 45.7%, p < 0.001) and had higher J‐CTO (2.76 ± 1.17 vs. 2.37 ± 1.26, p = 0.008), PROGRESS‐CTO MACE (3.56 vs. 2.57, p < 0.001), Mortality (2.45 vs. 1.68, p < 0.001), Pericardiocentesis (2.74 vs. 1.87, p < 0.001), Acute MI (1.72 vs. 0.89, p < 0.001) and Perforation (3.21 vs. 2.19, p < 0.001) scores. There was no difference in technical success (80.5% vs. 87.2%, p = 0.086) or major cardiovascular adverse events (MACE) (2.4% vs. 2.0%, p = 0.700). LM CTO PCI patients with and without prior CABG surgery had similar technical success and MACE. The retrograde approach in prior CABG patients was more likely to be performed through saphenous vein grafts.ConclusionsLM CTO PCI is infrequently performed, is associated with high comorbidity burden and angiographic complexity but can be performed with high success and acceptable complication rates.