There are limited comparative data on the use of plaque modification devices during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared intravascular lithotripsy (IVL) with rotational atherectomy (RA) for lesion preparation in patients who underwent CTO PCI across 50 US and non-US centers from 2019 to 2024. Of 15,690 patients who underwent CTO PCI during the study period, 436 (2.78%) underwent IVL and 381 (2.45%) RA. Patients treated with IVL had more co-morbidities and more complex CTO lesions. Antegrade wiring was the most used initial and successful crossing strategy for lesions treated with both IVL and RA, although the retrograde approach was more frequently used in IVL cases. Procedure and fluoroscopy times, and air kerma radiation doses and contrast volumes, were greater in patients treated with RA than those treated with IVL. There were no significant differences between the groups in technical success (97.2% vs 95.3%, p = 0.20), procedural success (94.7% vs 91.8%, p = 0.14), and in-hospital major adverse cardiac events (MACEs) (3.0% vs 4.2%, p = 0.47). However, coronary artery perforations were more frequent in patients who underwent RA (9.5% vs 3.2%, p <0.001). Multivariable logistic regression analysis revealed that IVL compared with RA was not independently associated with technical success, procedural success, or in-hospital MACE. In patients who undergo CTO PCI, IVL is associated with similar in-hospital MACE, technical success, and procedural success but lower incidence of coronary artery perforation compared with RA.