Abstract Background Intravascular lithotripsy (IVL) is a promising balloon-based technique to treat calcified coronary lesions. The evidence of its use in LM disease is scarce and there are no studies reporting a comparison between IVL and conventional techniques for calcified lesions, especially in LM PCI that represented an exclusion criteria of the DISRUPT-CAD trials. Methods The aim of this study is to evaluate safety and efficacy of IVL to treat moderate-severe calcified LM disease from January 2018 to December 2022. We stratified our cohort into two groups 1) patients who underwent LM PCI with IVL treatment (bail-out or upfront) and 2) LM PCI with conventional techniques excluding IVL (cutting balloons, NC/OPN balloons, rotational atherectomy). Efficacy endpoint: device success and stent expansion evaluated either by intravascular imaging or angiographic criteria. Safety endpoint: peri-procedural complications (coronary dissection, perforation, no-slow flow, peri-procedural MI, pericardial effusion) and in hospital death or target vessel failure. Results 87 patients were enrolled, 43 (49.4%) underwent LM PCI with IVL (group A), while 44 (50.6%) were treated with conventional techniques (35 NC balloons, 7 RA, 2 cutting balloons). Intravascular imaging was performed in 69% of cases, the 2 groups were similar in terms of age (77.4±9.63, p=0.94), comorbidity, clinical presentation and angiographic characteristics. Both groups presented severe calcifications in terms of calcium length (11.9±10.3, p=0.87), arc (270° 144-350, p = 0.76, and thickness (1.3 ±0.7 p =0.99) assessed by intravascular imaging. IVUS calcium score was similar between 2 groups (1.53±0.7, p = 0.7). Target vessel was distal LM-proximal LAD in 56.6%. IVL most used balloon was 3.5mm (55%), followed by 4.00mm (38.2%). Impella CP was implanted to support 4 PCI and removed at the end of the procedure. Provisional stenting was performed in 55.1% of cases, while two-stents technique was used in 26.4% (mainly represented by DK-crush). Good stent expansion (>80%) was achieved in 85% of cases, with a certain prevalence for patients treated with IVL. Optimal stent expansion (>90%) was higher in patients treated with IVL (9 in group A vs 3 in group B), although it did not reach a statistically significative difference (p=0.06). No differences in terms of complications and peri-procedural myocardial infarction occurred between the two groups. Conclusions This is the first description of a comparison between IVL and conventional techniques in LM calcified PCI. IVL appeared to be safe and effective with good stent expansion and low rate of peri-procedural complications and in-hospital MACE. LM lesions treated with IVL appeared to reach greater stent expansion compared to other techniques, although it was not statistically significative. Certainly, further trials are warranted to establish longer term outcomes and the benefit of IVL over existing calcium-modification therapies.