The stent-artery interactions of different stent designs have implications for their clinical effects. We studied four different stent designs to compare their effects on arterial injury, cellular proliferation, neointima formation, and arterial dimensions. Eighteen nonatherosclerotic miniswine underwent random placement of 52 coronary stents (3.0 mm), including self-expanding nitinol stents (no postdilation; Radius, n = 13) and balloon-expandable stents (8 atm x 45 sec; Palmaz-Schatz, n = 13; BX, n = 12; and Multilink, n = 14). Cellular proliferation was determined by S-phase labeling with BrdU at 7, 14, and 28 days. Proliferation, injury scores, and arterial morphometry were blindly evaluated. All four stent designs had similar injury scores, cellular proliferation indexes (neointimal and medial), and adventitial areas. Nitinol stents resulted in a twofold increase in neointimal area and thickness in 28-day vessels (P = 0.002). However, lumen area was similar for all stent designs because of an offsetting expansion in vessel area in nitinol stents (20% greater than balloon-expandable stents) occurring between 7 and 14 days after stent deployment (P = 0.03). Reduced neointimal cell density in nitinol stents (20% less than balloon-expandable stents, P = 0.012) suggests that extracellular matrix expansion accounts for the larger neointima in nitinol stents. Self-expansion of nitinol stents within normal porcine arteries results in a similar degree of arterial injury compared to balloon-expandable stent designs. Progressive enlargement of nitinol stents between 7 and 14 days after deployment is associated with the development of a larger, matrix-rich neointima, with a preserved lumen area. Cathet Cardiovasc Intervent 2001;53:420-425. Published 2001 Wiley-Liss, Inc.