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Use of intravascular lithotripsy (IVL) for treating peri-stent calcification is increasing. However, this indication remains 'off-label'. We aimed to investigate the efficacy and clinical outcomes of in-stent IVL. Patients from five European centers who underwent in-stent IVL were included between 2019 and 2023. Demographic, clinical, procedural and follow-up data were collected from electronic hospital records. Angiographic and intracoronary imaging (ICI) data were analyzed in a centralized core-laboratory. Of 101 patients (71.2 ± 9.2 years), 56(55 %) received in-stent IVL for late stent failure (median 109 days post-PCI) due to calcific neoatherosclerosis or extra-stent calcification(late-IVL), while 45(45 %) underwent bail-out IVL due to stent infraexpasion (immediate-IVL). Both late-IVL and immediate-IVL significantly improved angiographic %diameter stenosis (73.7[59.6–89.8]% to 16.4 [10.4–26.9]%; p < 0.0001 and 28.6[22.5–43.3]% to 14.1[10.3–29.4]%;p < 0.0001, and minimum lumen area (MLA) (3.4 ± 1.2 to 8.6 ± 2.5 mm2; p < 0.002 and 5.4 ± 1.9 to 7.3 ± 1.9;p < 0.0001).Device(98 %) and procedural success(80 %) were high. MACE rates in-hospital (2 %), 30-days (3 %),6-months(5 %) and 1-year(7 %) were low and comparable in both groups. Acute diameter gain was lower in immediate-IVL (2.1 ± 0.7 mm vs. 0.5 ± 0.4 mm;p < 0.0001). This, however, was explained by significant differences in pre-IVL angiographic and ICI parameters (%diameter stenosis 73.7[59.6–89.8] vs. 28.6[22.5–43.3]%; p < 0.0001 and MLA (3.4 ± 1.2 vs 5.4 ± 1.9 mm2; p < 0.0001), whereas post-IVL percentage diameter stenosis (16.4(10.4–26.9) vs. 14.1(10.3–29.4); p = 0.914) and MLA (8.6 ± 2.5vs. 7.4 ± 1.9 mm2; p = 0.064) in late- and immediate-IVL were comparable. IVL in-stent due to peri-stent calcification is an effective strategy, both late and immediately after stent implantation. Overall, MACE rates at short- and mid-term were low and comparable in both groups, although clinical findings should be taken with caution. • IVL in-stent is an effective strategy, with high procedural success rate. • Similar results apply both for IVL late and immediately after stent implantation. • Overall, MACE rates at short- and mid-term were low. [ABSTRACT FROM AUTHOR]