Introduction: The effect of radiation on the inhibition of neointima formation after angioplasty seems to be through cell cycle arrest and induction of apoptosis of vascular smooth muscle cells (VSMCs). NF-kB, however, promotes cell survival against external stress such as radiation, and thus, VSMCs are known to be relatively radio-resistant. The aim of the study was to investigate whether NF-kB inhibition enhances the antiproliferative effects of radiation on VSMCs. Materials and methods: Transfection of NF-kB decoy oligonucleotides was used to evaluate the effects of NF-kB inhibition on irradiated VSMCs. The extent of cellular viability and proliferation was determined by MTT assay after gamma-ray irradiation using 137-Cs. Flow cytometry analysis was performed to evaluate the effects of NF-kB inhibition on VSMC apoptosis and the cell cycle. Results: Irradiation induced the nuclear translocation of NF-kB p65 in VSMCs. As expected, irradiation resulted in increased apoptosis (5.14%짹1.12 vs. 13.33%짹2.08 for non-irradiated vs 16-Gy radiation, p<0.05) of VSMCs and G1 and G2 arrest of the cell cycle. NF-kB inhibition potentiated the antiproliferative effects of radiation at all doses (MTT survival assay at 48 hours after irradiation: 1.24짹0.16, vs. 1.99짹0.27 for 8-Gy radiation combined with NF-kB decoy transfection vs. 8-Gy radiation without NF-kB inhibition, p<0.05). Flow cytometry showed that NF-kB significantly increased apoptosis in irradiated VSMCs (26.29%짹7.43 vs. 13.33%짹2.08 for 16-Gy radiation with NF-kB inhibition vs non inhibition, p<0.05) while its effect on the cell cycle was minimal. Conclusion: NF-kB inhibition potentiates the antiproliferative effects of gamma-ray irradiation, which suggests the possibility of adjunctive gene therapy using NF-kB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.