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Coronary calcification is common and increases the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined the impact of calcium on procedural outcomes of 13,079 CTO PCIs performed in 12,799 patients at 46 US and non-US centers between 2012 and 2023. Moderate or severe calcification was present in 46.6% of CTO lesions. Patients whose lesions were calcified were older and more likely to have had prior coronary artery bypass graft surgery. Calcified lesions were more complex with higher J-CTO score (3.0 ± 1.1 vs. 1.9 ± 1.2; p < 0.001) and lower technical (83.0% vs. 89.9%; p < 0.001) and procedural (81.0% vs. 89.1%; p < 0.001) success rates compared with mildly calcified or non-calcified CTO lesions. The retrograde approach was more commonly used among cases with moderate/severe calcification (40.3% vs. 23.5%; p < 0.001). Balloon angioplasty (76.6%) was the most common lesion preparation technique for calcified lesions, followed by rotational atherectomy (7.3%), laser atherectomy (3.4%) and, intravascular lithotripsy (3.4%). The incidence of major adverse cardiovascular events (MACE) was higher in cases with moderate or severe calcification (3.0% vs. 1.2%; p < 0.001), as was the incidence of perforation (6.5% vs. 3.4%; p < 0.001). On multivariable analysis, the presence of moderate/severe calcification was independently associated with lower technical success (odds ratio, OR = 0.73, 95% CI: 0.63–0.84) and higher MACE (OR = 2.33, 95% CI: 1.66–3.27). Moderate/severe calcification was present in nearly half of CTO lesions, and was associated with higher utilization of the retrograde approach, lower technical and procedural success rates, and higher incidence of in-hospital MACE. • Moderate/severe calcification: • is present in nearly half of chronic total occlusion (CTO) lesions • requires more frequent use of the retrograde approach • requires more frequent use of intravascular ultrasound (IVUS) and advanced plaque modification techniques • is associated with lower technical and procedural success, and higher major adverse cardiovascular events (MACE) [ABSTRACT FROM AUTHOR]