Restenosis in peripheral vessels caused by intimal hyperplasia after stent implantation, PTA, atherectomy or laser treatment ranged up to 40%. In order to avoid the hyperplastic reaction with restenosis we treated our patients with prophylactic endovascular afterloading therapy after failure of PTA in case of recurrent stenosis. We had 30 patients with up to 4 recurrent stenoses between 4 and 7 months due to intimal hyperplasia in the stented area. To minimize the reocclusion rate we performed an irradiation with 12 Gy surface dose in one session using the endovascular afterloading method with 192 Iridium HDR following re-PTA in the stented vessel segment. The longest follow up is 68 months. The histological analyses of tissue years after irradiation showed a thinner, more compact cellular layer of the myofibroblasts with less myxoid degeneration between the cells compared to intimal hyperplasia and plaques in not irradiated vessel segments. The follow up showed a significant effect of endovascular radiotherapy. The histological findings after irradiation were a diminished growth in the cellular population of the analysed vessel wall compared to not irradiated vessel wall segments of the same patient. These findings may be explained by a reduced migration and mitosis rate of myofibroblastic cells after irradiation. The method may be an interesting alternative to stent implantation alone. Even vessel segments like the Hunter's channel will be patent for a long time follow up. Because of the steep decay in the dose using the endovascular irradiation method with 192 iridium HDR, the method can be used with minimal risk for the surrounding tissue.