BACKGROUND AND OBJECTIVES: Brachytherapy is a promising method in the prevention and treatment of coronary stent restenosis. We sought to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 (166Ho) in a porcine coronary stent restenosis model. Materials and Methods: A radioisotope of (166Ho) was coated on the balloon surface using a polyurethane coating (20 Gy in 0.5 mm depth). Stent overdilation injuries were performed in two coronary arteries in 8 pigs. Four weeks after the stent overdilation injury, radiation therapies were performed using a control balloon dilation in one coronary artery (Group I:n = 8) and a 166Ho-coated balloon in the other coronary artery in each pig (Group II:n = 8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after the therepy was administered. RESULTS: Laboratory findings did not differ significantly between the pre-treatment baseline and the measurements taken after radiation. On quantitative coronary angiogram, the coronary artery diameters were not significantly different between the two groups before stenting or at 4 and 8 weeks after stenting. On histopathologic analysis, injury score, internal elastic lamina area and lumen area did not differ significantly between the two groups. The neointimal area was 1.78 +/- 0.11 mm2 in group I and 1.36 +/- 0.12 mm2 in group II (p=0.017), and the histopathologic area of stenosis was 35.1 +/- 1.6% in Group I, 27.6 +/- 1.9% in Group II (p=0.005). CONCLUSION: A treatment of beta-radiation in a stented porcine coronary artery using radioactive Ho-166 coated balloon inhibits stent restenosis without any side effects.