Donor vessel injury is a potentially life-threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined the incidence and outcomes of donor vessel injury among 12,349 CTO PCIs performed between 2012 and 2022 in a large multicenter CTO PCI registry. The incidence of donor vessel injury was 0.5% (n=59). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated with donor vessel injury were more complex with higher J-CTO score (3.0 ± 1.1 vs. 2.4 ± 1.3; p<0.001) and lower procedural success rate (71% vs. 85%; p=0.003). The retrograde approach was used more commonly among cases complicated with donor vessel injury (68% vs. 31%; p<0.001). The incidence of major adverse cardiovascular events (MACE) was significantly higher in cases with donor vessel injury (22% vs. 1.9%; p<0.001). Left ventricular assist device was used in 13 patients (22%) with donor vessel injury. Of the 59 patients with donor vessel injury, 8 patients (11%) experienced acute myocardial infarction (MI), and 4 patients died (6.8%). CTO PCIs complicated with donor vessel injury required longer procedure time and fluoroscopy time, higher air kerma radiation dose, and larger contrast volume. Donor vessel injury occurred in 0.5% of CTO PCIs performed by experienced operators, and was associated with lower procedural success and higher adverse clinical outcomes, such as death and acute MI.