This study tested the combination of vascular brachytherapy (VBT) and self-expanding Wallstent implantation in coronary lesions of patients at high risk for restenosis as assessed angiographically by quantitative coronary analysis and by 3-dimensional intravascular ultrasound analysis. Twenty-nine “de novo” lesions were managed with a self-expanding stent alone (n = 19) or with a self-expanding stent after β-VBT (n = 10) in 27 patients who had been identified by high levels of plasma angiotensin-converting enzyme as being prone to myointimal growth after stent implantation. At 6 months, the increase in stent strut diameter was similar in the 2 groups by quantitative coronary analysis and 3-dimensional intravascular ultrasound (Δ mean stent strut diameter −0.33 ± 0.3 vs −0.40 ± 0.3 mm, p = 0.5; Δ stent area −11.8 ± 6.1 vs −12.0 ± 6.1 mm², p = 0.9; Δ stent volume −96.9 ± 112 vs −83.5 ± 73 mm³, p = 0.7; for groups treated with VBT and self-expanding stents and only self-expanding stents, respectively). In-stent neointimal proliferation was decreased in the group treated with VBT and self-expanding stents (minimal luminal diameter 2.5 ± 0.8 vs 1.88 ± 0.8 mm, p = 0.04) by quantitative coronary analysis (minimal luminal area 6.7 ± 2.5 vs 4.1 ± 1.9 mm², p = 0.01), by intravascular ultrasound, and proliferation volume (84.6 ± 66.4 vs 159.2 ± 103.5 mm³, p = 0.05) by 3-dimensional intravascular ultrasound. Positive vessel and luminal remodelings were observed in 50% of the group treated with VBT and self-expanding stents and in 11% of the group treated only with self-expanding stents (p = 0.02). The combined use of VBT and self-expanding stents is a novel approach that enlarges vascular lumen by preventing vessel constriction and neointimal proliferation. The feasibility and good results of this experimental approach suggest that the simultaneous use of these 2 technologies may be an interesting alternative for difficult vascular districts with high restenosis rates, such as peripheral circulation in the lower limbs.