We investigated the 2-year clinical follow-up results as well as 6-month angiographic and clinical follow-up results of intracoronary radiation therapy using a rhenium-188-diethylene triamine penta-acetic acid ((188)Re-DTPA)-filled balloon system. The study comprised of 161 patients with significant de novo (83%) or in-stent restenosis (17%) lesions. Irradiation to deliver 17.6 Gy at a depth of 1.0 mm into the vessel wall was carried out after successful intervention. At 6-month follow-up, binary restenosis developed with significantly lower frequency in the radiation group than in the control group (24.3% vs. 46.3%; P = 0.009), although target lesion revascularization rate did not show significant benefit. At 2-year follow-up, cumulative target lesion revascularization rate was not significantly different between radiation group (n = 86) and control group (n = 75; 20.0% vs. 26.0%; P = 0.368). The rate of major adverse cardiac events including death, myocardial infarction, and target lesion revascularization did not show significant difference between two groups either (22.3% vs. 30.1%; P = 0.266). In conclusion, although significant reduction in restenosis rate was noted at 6-month angiographic follow-up, intracoronary radiation therapy mostly in patients with de novo lesion did not show significant clinical benefit in 6-month and 2-year follow-up results. The benefit was noted only in a small subgroup of patients with in-stent restenosis.