Restenosis is the limiting entity after percutaneous coronary angioplasty. Vascular brachytherapy for the treatment of in-stent restenosis has been shown to reduce the repeat restenosis rate and the incidence of major adverse events in several randomized trials. Besides the beneficial effects, brachytherapy yielded some unwanted side effects. The development of new stenoses at the edges of the target lesion treated with radiation is termed edge effect. It occurs after afterloading brachytherapy as well as after implantation of radioactive stents. It is characterized by extensive intimal hyperplasia and negative remodeling. As contributing factors the axial dose fall-off, inherent to all radioactive sources, and the application of vessel wall trauma by angioplasty have been identified. The combination of both factors, by insufficient overlap of the radiation length over the injured vessel segment, has been referred to as geographic miss. It has been shown to be associated with a very high incidence of the edge effect. Avoidance of geographic miss is strongly recommended in vascular brachytherapy procedures. Late thrombosis after vascular brachytherapy is of multifactorial origin. It comprises platelet recruitment, fibrin deposition, disturbed vasomotion, non-healing dissection and stent malapposition predisposing to turbulent blood flow. The strongest predictors for late thrombosis are premature discontinuation of antiplatelet therapy and implantation of new stents during the brachytherapy procedure. With a consequent and prolonged antiplatelet therapy, the incidence of late thrombosis has been reduced to placebo levels. Edge effect and late thrombosis represent unwanted side effects of vascular brachytherapy. By means of a thorough treatment planning and prolonged antiplatelet therapy their incidences can be largely reduced. With regard to the very favorable net effect, they do not constitute relevant limitations of vascular brachytherapy.