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Background The aim of this study was to assess the safety and effectiveness of intravascular lithotripsy (IVL) in treating eccentric calcified coronary lesions. Methods Between December 2015 and March 2019, 180 patients were enrolled in the Disrupt CAD I and CAD II studies across 19 sites in 10 countries. Patient-level data were pooled from these two studies (n = 180), within which 47 eccentric lesions (26%) and 133 concentric lesions were identified. Results Clinical success, defined as residual stenosis p = 1.0). There were no perforations, abrupt closure, slow flow or no reflow events observed in either group, and there were low rates of flow-limiting dissections (Grade D–F: 0% eccentric, 1.7% concentric; p = 0.54). Final acute gain and percent residual stenosis were similar between the two groups. Final residual stenosis of 8.6 ± 9.8% in eccentric and 10.0 ± 9.0% (p = 0.56) in concentric stenosis confirms the significant effect of IVL in calcified coronary lesions. Conclusion In this first report from a pooled patient-level analysis of coronary IVL from the Disrupt CAD I and CAD II studies, IVL use was associated with consistent improvement in procedural and clinical outcomes in both eccentric and concentric calcified lesions.