Background: Severe femoropopliteal calcification increases endovascular complexity and is associated with impaired luminal gain, vessel injury, restenosis and bailout stenting. Pulsatile intravascular lithotripsy (PIVL) delivers hydraulic pressure waves through a non-compliant balloon. POWER PAD I evaluated first-in-human feasibility and safety of PIVL in calcified femoropopliteal disease. Methods: POWER PAD I was a prospective, single-arm, two-centre study. Adults with Rutherford 2-4 symptomatic peripheral arterial disease and calcified superficial femoral or popliteal lesions underwent PIVL, with adjunctive therapy as indicated. Angiographic and duplex outcomes were core-lab assessed; adverse events independently adjudicated. Results: Nine patients underwent treatment of 20 lesions. Mean age was 76.2 ± 12.6 years, five were male, 19 lesions were severely calcified and five were chronic total occlusions. Device and procedural success were achieved in 8/9 patients, and technical success in 9/9. All 15 balloons were delivered, inflated, deflated and retrieved. One balloon ruptured after therapy delivery, causing automatic system shut-off without clinical sequelae. Mean diameter stenosis improved from 76.5 ± 18.0% to 28.1 ± 6.9% after PIVL and 20.6 ± 5.8% after adjunctive therapy. Mean minimal luminal diameter increased from 1.3 ± 1.0 mm to 3.8 ± 0.5 mm after PIVL and 4.3 ± 0.6 mm at final angiography. There was no perforation, distal embolisation, thrombus, abrupt closure, no-reflow, bailout stenting, or grade D or higher dissection. Freedom from clinically driven target-lesion revascularisation was 100% at 30 days and 6 months, with one event by 12 months. Conclusions: In this first-in-human study, PIVL was feasible for heavily calcified femoropopliteal lesions, achieving substantial acute luminal gain without severe vessel-wall complications or bailout stenting. Larger controlled studies with longer follow-up and intravascular imaging are warranted.