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Background Fifteen percent of patients with coronary artery disease undergoing angiography have a chronic total occlusion (CTO). The current study aimed to investigate the long‐term prognosis after successful and unsuccessful CTO percutaneous coronary intervention (PCI) compared with PCI for non‐CTO lesions. Methods and Results The current study was designed as an observational, region‐wide, register‐based cohort study enrolling all patients undergoing PCI in the Central Region of Denmark in 2009 to 2019. Patients were stratified into non‐CTO, successful CTO, and unsuccessful CTO revascularization. Patients were followed until an event or January 1, 2022. The primary end point was all‐cause mortality. In 21 141 patients enrolled, 2108 underwent CTO PCI. Clinical presentation was acute coronary syndrome in 11 879 patients and chronic coronary syndrome in 7887 patients. After a median of 5.7 years (interquartile range, 3.3–8.8), long‐term all‐cause mortality was higher after CTO PCI compared with non‐CTO PCI, but the difference was statistically insignificant when adjusting for clinical factors (unadjusted hazard ratio [HR], 1.19 [95% CI, 1.09–1.29], adjusted HR, 1.08 [95% CI, 0.97–1.20]; P=0.165). After successful CTO PCI, no difference compared with non‐CTO PCI was observed (unadjusted HR, 0.99 [95% CI, 0.90–1.10], adjusted HR, 0.99 [95% CI, 0.87–1.12]; P=0.873). After unsuccessful CTO PCI, long‐term all‐cause mortality was higher than non‐CTO PCI (unadjusted HR, 1.82 [95% CI, 1.59–2.08], adjusted HR, 1.35 [95% CI, 1.13–1.63]; P |