Acute stent thrombosis remains a major concern of coronary stent implantation. Animal studies using stents do not adequately mimic this clinical problem, since stent placement is rarely associated with acute closure. The purpose of this study was to develop and characterize a porcine model of stent thrombosis. Improved understanding through such a model may be useful toward preventing and treating acute stent closure. Whole blood was drawn from domestic crossbred swine one day before study. Platelets were isolated, labeled with 111-In tropolone, and reinjected within 18 hr of the study. Bilateral carotid arteries were exposed, and severe injury induced by a series of mechanical crushes. This method produced histologic injury similar to human coronary angioplasty, with medial disruption and large dissections protruding into the lumen. Stenting was performed in standard fashion with 3.5-mm JJIS stents. Local platelet deposition was measured and recorded as 111-In radioactivity using a miniaturized scintillation detector (Dosimeter Corp.) mounted directly at the artery injury site. This measurement was made in real time at 1-min intervals. Similarly, volumetric blood flow was measured in real time by Doppler flowmeter. Eighteen arteries of nine pigs were studied. In nine arteries from nine pigs, crush injury only was performed and monitored. In the contralateral artery, crush injury was followed immediately by placement of a 3.5-mm Palmaz-Schatz (coronary) stent. Blood flow decreased rapidly following injury in both groups and followed a cyclic pattern. Eight arteries of the crush alone and two arteries of the crush plus stent groups were totally occluded 1 hr after crush. 111-In counts normalized to baseline were significantly higher at 1 hr in both groups compared to baseline; in the stented group, counts were higher than in the unstented group. Blood flow was higher in the stented group than in unstented group for 1 hr. Histopathologic observation of the thrombi forming in both crush-only and crush-stent injuries showed severe medial dissections with obstructing medial flap formation. The thrombi forming in both groups were highly platelet rich. This model of stent and arterial thrombosis showed rapid formation of platelet-rich thrombus, cyclic blood flow variations, and acute occlusion in 20% of cases. Stent placement at arterial injury sites is associated with thrombus that is predominantly platelet rich. Stent placement at injury sites enhances platelet deposition over crush injury alone. Despite greater numbers of platelets, as shown by increased 111-In counts, stenting improved vessel patency. These were likely due to higher volumetric blood flow, continuous deposition, and embolization of labeled platelets.