BACKGROUND: Heparin has been shown to reduce intimal thickening after arterial wall injury by inhibiting vascular smooth muscle cell proliferation and migration. The authors studied the acute and long-term results after local delivery of heparin after balloon angioplasty for in-stent restenosis. METHODS AND RESULTS: Forty-seven in-stent restenosis cases, 32 of them longer than 1 cm, were enrolled. After angioplasty local heparin delivery was performed using the Dispatch coronary infusion catheter (Scimed Life Systems/Boston Scientific Corp, Natick, MA, USA); the infusion rate was 99.9 ml per hour and a target dosage of 4000 iu heparin per site was intended to be delivered. In nine cases (19.15%) heparin delivery had to be stopped because of ischemia. One patient died six days after intervention. After a follow-up interval of 6-12 months target vessel revascularization rate was 28.26%. CONCLUSIONS: For the protocol used ischemia occurred more often than previously reported. Considering the fact that most patients had diffuse in-stent restenosis, the target revascularization rate at follow-up was acceptable.