It is well-known and often argued by practicing physicians that the highly selected patients in the randomized controlled trials (RCTs) of lower extremity arterial disease do not often match the patients encountered in real-world practice. 1 Therefore, it is imperative to review and understand real-world studies to see if the proof of concept is carried on from the RCTs to the ground reality. Drug-coated balloon (DCB) angioplasty for femoropopliteal arterial disease can be considered a landmark endovascular treatment strategy in the field of symptomatic lower extremity occlusive disease. 1,2 In the October 2020 issue of the JEVT, Torsello et al 4 present the 3-year outcomes of the IN.PACT Global study of DCB angioplasty in a real-world femoropopliteal cohort. To put these results into perspective, we need to thread back into history. The IN.PACT Global study 2 (ClinicalTrials.gov identifier NCT01609296) was designed to see how DCB angioplasty fared in real-world, complex femoropopliteal disease, including long lesions (≥15 cm), in-stent restenoses (ISR), chronic total occlusions (CTOs) ≥5 cm long, calcified lesions, and TransAtlantic Inter-Society Consensus (TASC) C/D lesions, as well as in the setting of poor runoff, popliteal artery involvement, and bilateral disease. The clinical presentation in the 1535 participants was consistent with claudication and chronic limb-threatening ischemia (CLTI). The first publication from the IN.PACT Global study, 5 in a 131-patient ISR subgroup (mean lesion length 17.17 cm, 34% CTOs, 59.1% with calcifications, 88% with diffuse ISR, and 42% with TASC C/D lesions), 5 found a 1-year clinically-driven target lesion revascularization (CD-TLR) rate of 7.3%, with estimated primary patency of 88.7%. The primary safety outcomes were achieved in 92.7%. The 2-year outcomes reported by Micari et al 6 on 1406 patients (1773 lesions) in the clinical cohort study were promising, with estimated freedom from CD-TLR as high as 83.3% and meeting the composite safety endpoint in 81.7%. It is reassuring to know that these positive results were sustained through 36 months, 4 with estimated freedom from CD-TLR at 76.9% and a composite safety endpoint of 75.6%. Notably, the death rate climbed from 7.0% at 24 months to 11.6% at 36 months.