We sought to examine the impact of calcific deposits on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The outcomes of 1,476 consecutive CTO PCIs performed in 1,453 patients (65.5 ± 10 years, 85% male) between 2012 and 2016 at 11 US centers were evaluated. Moderate or severe quantity of calcium was present in 58% of target lesions. Calcified lesions were more tortuous and more likely to have proximal cap ambiguity and interventional collaterals. PCI of moderately/severely calcified CTOs more often required use of the retrograde approach (54% vs 30%, p <0.001) and was associated with longer procedure and fluoroscopy time and higher air kerma radiation dose and contrast volume. Moderate/severe quantity of calcium was associated with lower technical (86.6% vs 93.8%, p <0.001) and procedural (84.4% vs 92.7%, p <0.001) success rates and higher incidence of major adverse cardiac events (3.7% vs 1.8%, p = 0.033). On multivariate analysis, the presence of moderate/severe quantity of calcium was not independently associated with technical success. Balloon angioplasty was the most common lesion preparation technique for calcified lesions, followed by rotational atherectomy and laser. To conclude, in a contemporary, multicenter registry, moderate/severe calcific deposits were present in 58% of attempted CTO lesions and were associated with higher use of the retrograde approach, lower success, and higher complication rates. However, on multivariable analysis, the amount of calcium was not independently associated with technical success.