BACKGROUND: In drug-eluting stent (DES) era, main concern about the DES was divided to ISR by neointimal hyperplasia and late stent thrombosis by delayed arterial healing. In this aspect, statin could be expected to have therapeutic potential in both aspects. Previous studies have shown that, in addition to the favorable effects on lipid levels, combined therapy with ezetimibe plus simvastatin produced significant reductions in C-reactive protein relative to statin monotherapy. OBJECTIVES: We examined the effects of ezetimibe/simvastatin on neointimal hyperplasia, inflammatory reaction, and endothelization for arterial healing after DES implantation in a porcine coronary restenosis model. METHODS: Pigs were randomized into two groups in which the coronary arteries (23 pigs, 28 coronaries in ezetimibe/simvastatin group, 15 coronaries in no ezetimibe/simvastatin group) had either a sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES). Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Histopathologic analysis was assessed at 28 days after stenting. RESULTS: In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337짹227 cells vs. 443짹366 cells, p=0.292). Furthermore, the percent of inflammatory cell among the total cell in neointima was not different between two groups (5.2짹2.8% vs. 5.6짹4.0%, p=0.73). Neointima area was significantly smaller (1.00짹0.49 mm2 vs. 1.69짹0.98 mm2, p=0.004) and percent area stenosis was significantly lower (23.3짹10% vs. 39짹19%, p=0.001) in ezetimibe/simvastatin group compared with control group. There was no significant differences in fibrin score (1.99짹0.79 vs. 1.81짹0.88, p=0.49), endothelial score (1.75짹0.66 vs. 1.80짹0.59, p=0.79), and the percent of endothelium covered lumen (43짹21 % vs. 45짹21 %, p=0.84) between two groups. CONCLUSIONS: Combined therapy with ezetimibe plus simvastatin may inhibit neointimal hyperplasia but does not inhibit inflammatory cell infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.