Background: Intracoronary radiation therapy(IRT) prevents recurrent in-stent restenosis, but its very long-term safety and efficacy remains uncertain. In the present study, very long-term clinical outcome of IRT using the ¹⁸⁸Re-diethylene-triamine-penta-acetic-acid(DTPA)-filled balloon system was evaluated. Methods: 187 patients were randomly assigned to either radiation group(RG)(N=104) or control group(CG)(N=83) after successful catheter-based treatment of either de novo or restenotic lesions. The ¹⁸⁸Re-DTPA-filled balloon system was designed to deliver 17.6Gy to 1.0-mm tissue depth. Five-year clinical outcomes were analyzed. Results: Angiographic restenosis was significantly reduced with IRT at 9 months(RG 18.9% vs CG 45.9%, p<0.001), but the incidence of major adverse cardiac events(MACE) including death, myocardial infarction (MI), and target-vessel revascularization(TVR) by 5 years showed no difference(RG 35% vs CG 38%, p=0.88). Event free survival curves also showed no difference (p=0.69). In the restenotic subgroup(N=37), the MACE within 5 years was significantly reduced(RG 23% vs 64%, p=0.03)(table1) and event free survival curves showed significant benefit(p=0.008) with IRT. But angiographically proven late total thrombotic occlusions were occurred in 3 radiation group patients at 31, 50, and 51months after IRT, which resulted in non-fatal myocardial infarction, fatal myocardial infarction, and fatal myocardial infarction respectively. Conclusions: Although IRT using ¹⁸⁸Re-DTPA-filled balloon system showed durable clinical benefits for restenotic lesions up to five years, fatal late thrombotic occlusions occurred in very late periods of IRT. Therefore, life-long dual anti-platelet therapy may be indicated in patients with radiation therapy.