Endovascular brachytherapy with gamma-radioactive source ((192)iridium ) significantly reduces the restenosis after femoropopliteal angioplasty for both de novo and recurrent lesions. Increased arterial patency after additional stenting and brachytherapy was also achieved with the same approach. This was found as a result of single-center studies performed in Frankfurt, Germany, Vienna, Austria, and Bern, Switzerland. However, until recently, only one multicenter investigation was published that also underlined this positive effect of brachytherapy. A definitive role of radiotherapy in restenosis prevention should be established after the results of three multicenter, phase III trials (ie, Paris, Vienna-3, and Swiss) are presented in early 2003. These investigations recruited approximately 630 patients with recurrent and de novo lesions without stent placement. Another important phase III study, the results of which are also expected at the beginning of 2003, is the Vienna-5 trial. This study had the same inclusion criteria as the Paris and Vienna-3 trials, but angioplasty was combined in all patients with stenting. The patients were then randomized for brachytherapy or sham irradiation. Endovascular brachytherapy has shown to be a safe treatment modality. The only clinically relevant impediment was the late sudden thrombosis or occlusion that occurred after stenting and radiation. These events can present up to 1 year after brachytherapy, and in some cases even later. Prolonged antiplatelet medication with clopidogrel (at least 12 months) has solved this problem completely. No other major adverse effects were seen. If gamma radiation is used, the patients must be transported after intervention to the brachytherapy suite, owing to radiation safety regulations. Although no negative consequences during transportation were observed in all performed studies, this represents an additional risk. To shorten the whole procedure, studies using beta sources ((32)phosphorus, (90)strontium) are ongoing, whereas those with beta-radioactive sources of brachytherapy can be performed in the catheterization laboratory. Emerging approaches using drug-eluting stents with antiproliferative substances such as rapamycin and paclitaxel are being investigated as well; however, the safety and efficacy for restenosis prophylaxis must be proven in large clinical trials.