BACKGROUND AND OBJECTIVES: Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction and preventing atherosclerosis-related diseases. We evaluated the affect of ALA on stent restenosis in a porcine model. MATERIALS AND METHODS: The First experiment: Balloon overdilation injuries were performed in two coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stents were randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group II was the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after stenting in both experiments. RESULTS: The First experiment On histopathologic analysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. The neointimal area was 7.3+/-0.9 mm2 in the control group and 2.2+/-1.1 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 75.9+/-8.5% in the control group and 23.5+/-10.5% in the ALA group (p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantly different between the two groups. The neointimal area was 7.4+/-1.1 mm2 in the control group and 1.4+/-0.8 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6+/-10.9% in the control group and 15.6+/-7.6% in the ALA group (p<0.001). CONCLUSION: Both a high dose of oral ALA and ALA coated stents inhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model.