We report the first case of in-stent re-stenosis in a sirolimus-coated stent in a heart transplant recipient with allograft vasculopathy. A 54-year-old male transplant recipient with new lesions in the left anterior descending artery detected during a routine surveillance catheterization was treated with two sirolimus-coated stents. Three months later he presented with dyspnea on exertion, and a repeat left heart catheterization demonstrated a focal area of in-stent stenosis in the proximal stent, which was treated with a cutting balloon.