Background: There is limited information about the frequency and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in anomalous coronary arteries (ACA). Methods: We examined the clinical and angiographic characteristics and procedural outcomes of CTO PCI in ACA among 14,173 patients who underwent 14,470 CTO PCIs at 46 US and non-US centers between 2012 and 2023. Results: Of 14,470 CTO PCIs, 36 (0.24%) were CTO PCIs in an ACA. ACA patients had similar baseline characteristics as those without an ACA. The type of ACA in which the CTO lesion was found were as follows: anomalous origin of the right coronary artery (ARCA) (17, 48.5%), anomalous origin of left circumflex coronary artery (9, 25.7%), left anterior descending artery and left circumflex artery with separate origins (4, 11.4%), anomalous origin of the left anterior descending artery (2, 5.7%), dual left anterior descending artery (2, 5.7%) and woven coronary artery 1 (2.8%). The Japan CTO score was similar between both groups (2.17 ± 1.32 vs 2.38 ± 1.26, p = 0.30). The target CTO in ACA patients was more likely to have moderate/severe tortuosity (44% vs 28%, p = 0.035), required more often use of retrograde approach (27% vs 12%, p = 0.028), and was associated with longer procedure (142.5 min vs 112.00 min [74.0, 164.0], p = 0.028) and fluoroscopy (56 min [40, 79 ml] vs 42 min [25, 67], p = 0.014) time and higher contrast volume (260 ml [190, 450] vs 200 ml [150, 300], p = 0.004) but had similar procedural (91.4% vs 85.6%, p = 0.46) and technical (91.4% vs 87.0%, p = 0.59) success. No major adverse cardiac events (MACE) were seen in ACA patients (0% [0] vs 1.9% [281] in non-ACA patients, p = 1.00). Two coronary perforations were reported in ACA CTO PCI (p = 0.7 vs. non-ACA CTO PCI). Conclusions: CTO PCI of ACA comprise 0.24% of all CTO PCIs performed in the PROGRESS CTO registry and was associated with higher procedural complexity but similar technical and procedural success rates and similar MACE compared with non-ACA CTO PCI.