Background <p>Intravascular lithotripsy (IVL) emerged for the treatment of coronary artery calcification with encouraging safety and effectiveness rates in previous trials. Knowledge about the in-hospital safety of IVL in comparison to frequently used plaque modification techniques remains limited.</p> Objectives <p>The aim of this study was to assess the in-hospital outcomes of IVL in comparison to rotational atherectomy (RA) and cutting/scoring balloons (C/S).</p> Methods <p>A total of 51,921 isolated PCI procedures of patients who underwent planned coronary angiography with IVL, RA or C/S between 2019 and 2023 were extracted from a German nationwide registry. Analyses of the average treatment effect were carried out employing a double-robust estimator using machine learning algorithms.</p> Results <p>Compared to IVL, adjusted procedural relative risk of in-hospital mortality was significantly higher for RA (RR 1.72; 95% CI: 1.24 – 2.38, <i>p</i> = 0.001) and C/S (RR 1.50; 95% CI: 1.08 – 2.08, <i>p</i> = 0.015), while safety parameters such as stroke, severe bleeding and acute kidney injury were comparable. The adjusted risk of shock (RR 1.57; 95% CI: 1.20 – 2.04, <i>p</i> = 0.001) and pericardial drainage (RR 1.95; 95% CI: 1.23 – 3.07, <i>p</i> = 0.004) was lower for IVL compared to RA but not to C/S. Further, IVL use was associated with a shorter adjusted length of hospitalization compared to RA (− 0.75&#xa0;days, <i>p</i> &lt; 0.001) and C/S (− 0.22&#xa0;days, <i>p</i> = 0.047).</p> Conclusion <p>IVL is associated with a favorable safety profile compared to RA and C/S and a more timely discharge of patients.</p> Graphical Abstract <p>In-Hospital Outcomes of Intravascular Lithotripsy compared to Rotational Atherectomy and Cutting/Scoring Balloon Angioplasty. AKIN: acute kidney injury, C/S: Cutting/Scoring balloon angioplasty, IVL: intravascular lithotripsy, RA: rotational atherectomy, RR: Relative Risk</p> Graphical Abstract <p></p>