Transplant vasculopathy significantly limits the survival of cardiac transplant patients and occurs in 50% of patients by 5 years posttransplant. We report our experience with six cardiac transplant patients who underwent intracoronary brachytherapy for in-stent restenosis. At four centers, six patients underwent intracoronary radiation for in-stent restenosis. All patients received extended antiplatelet therapy with clopidogrel and aspirin. Follow-up angiography was performed in all patients. Two of the six patients underwent subsequent target lesion revascularization. Patient 1 presented with total occlusion of her radiated lesion. She had a complex procedure requiring stenting for a dissection after the radiation dwell. Patient 2 had high-grade restenosis following brachytherapy. Patient 3 had a 50% restenotic lesion. Patients 4, 5, and 6 had follow-up angiography that showed no evidence of restenosis. There are few good options to treated accelerated transplant vasculopathy. Radiation therapy may be a viable option in this difficult patient population.