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AIMS: Histological restenosis models in animals have indicated that stent design has a significant impact on vessel trauma during stent implantation and on the amount of subsequent neointimal tissue proliferation. The impact of different stent designs on intimal hyperplasia in human atherosclerotic coronary arteries has not been determined. METHODS AND RESULTS: Angiographic and intravascular ultrasound studies were performed at the 6 month follow-up in 131 consecutive native coronary lesions of 131 patients treated with 50 Multi-Link stents, 40 InFlow stents and 41 Palmaz-Schatz stents. Lumen and stent cross-sectional areas (CSA) were measured at 1 mm axial increments. Mean intimal hyperplasia cross-sectional area (stent CSA-lumen CSA) and mean intimal hyperplasia thickness were calculated. Intravascular ultrasound demonstrated different levels of intimal hyperplasia proliferation for the three stents. Mean intimal hyperplasia thickness was 0.16+/-0.08 mm for Multi-Link stents, 0.26+/-0.19 mm for Palmaz-Schatz stents and 0.39+/-0.14 mm for Inflow stents (P<0.001). Multivariate analysis proved that stent type was the only independent predictor of intimal hyperplasia thickness at follow-up (P<0.001). CONCLUSION: Coronary stent design has a significant impact on subsequent intimal hyperplasia after implantation into atherosclerotic human coronary arteries. The corrugated ring design of the Multi-Link stent proved to result in less tissue proliferation at 6-month follow-up than the tubular slotted design of Palmaz-Schatz and InFlow stents.