Abstract Background The use of rotational atherectomy is currently prevalent in the treatment of left main coronary artery lesions. However, it often necessitates the use of a large burr to achieve adequate debulking, which, in turn, demands highly experienced operators. Intravascular lithotripsy (IVL) is a promising, user–friendly and increasingly employed technique for calcific plaque modification before percutaneous coronary intervention. Although in many cath labs it is now routinely used to treat lesions of the three main coronary arteries, there are still concerns regarding its use in the left main, primarily due to prolonged inflations required for its optimal efficacy. Methods We conducted a retrospective analysis using data from the multicenter retrospective Rolling Stone registry. The analysis involved data from 474 patients, with a stratification between IVL procedures involving left main coronary artery (46 patients) and those that did not (428 patients). The primary effectiveness endpoint was procedural success (defined as achieving residual stenosis < 20% with TIMI III flow); secondary endpoints included the rate of procedural related adverse events, in hospital adverse events and MACE rate at 30 days and 6 months. Results Between April 2018 and January 2023, a total of 474 underwent IVL procedures. Most patients presented with calcific lesion requiring lithotripsy in non–left main segments, while IVL was performed on the left main artery in 46 patients. No significative differences were found on baseline characteristics between LM and non–LM groups. Treatment of IVL–LM lesion was marked by a high procedural success rate (97.8%) and a low incidence of procedural and peri–procedural complications. However, there was a higher rate of contrast–induced acute kidney injury in patients treated in LM (6.5% vs. 1.6%, p=0.030), although no other differences for in–hospital outcomes were observed. Furthermore, there were no differences in 30–day and 6–month follow–up outcomes between the two groups. Conclusions This study suggests that employing intravascular lithotripsy in the left main coronary artery is not only a safe procedure but also produces excellent results comparable to its application in other coronary branches. This provides a substantial level of confidence in the safety and effectiveness of IVL when used in this specific context.