Backgroud: Neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA) is one of the major components of the process of restenosis. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) upon neointimal formation following PTCA in a rabbit model. Methods: PTCA was performed in the iliac arteries of 10 New Zealand white rabbits at 8 atm for 30 s, three times. An infusion of 500 μg Resten-NG (n=6) or saline (n=4) was delivered to the site at 2 atm via the outer balloon pores of the transport™ catheter over 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 6 months following PTCA. Results: After 6 months, animals were sacrificed and vessels were fixed in formalin, processed and stained with hematoxylin, eosin, and movat. Histological analysis revealed complete vascular healing in both groups of animals. Planimetry showed that intimal areas were 1.71±0.25 and 0.65±0.36 mm2 in the control and antisense delivery groups, respectively (P<.05). Conclusion: We conclude that local delivery of Resten-NG significantly inhibited neointimal thickening following PTCA in a rabbit for up to 6 months.