Although clinical trials using laser and thermal angioplasty devices have been underway, the effects of pulsed laser and thermal ablation of atherosclerotic plaque on surface thrombogenicity are poorly understood. This study examined the changes in platelet adherence and thrombus formation on freshly harvested atherosclerotic aorta segments from Watanabe-heritable hyperlipidemic rabbits after ablation by two pulsed laser sources (308-nm xenon chloride excimer and 2,940-nm erbium:yttrium-aluminum-garnet [YAG] lasers) and a prototype catalytic hot-tip catheter. Specimens were placed in a modified Baumgartner annular chamber and perfused with citrated whole human blood, followed by quantitative morphometric analysis to determine the percent surface coverage by adherent platelets and thrombi in the treated and contiguous control areas. Pulsed excimer laser ablation of plaque did not change platelet adherence or thrombus formation in the treated versus control zones. However, photothermal plaque ablation with a pulsed erbium:YAG laser resulted in a 67% reduction in platelet adherence, compared with levels in control areas (from 16.7 +/- 2.2% to 5.5 +/- 1.8%; p less than 0.005). Similarly, after plaque ablation using a catalytic thermal angioplasty device, there was a 74% reduction in platelet adherence (from 29.2 +/- 5.1% to 7.7 +/- 1.6%; p less than 0.005) and a virtual absence of platelet thrombi (from 8.6 +/- 2.3% to 0.03 +/- 0.03%; p less than 0.005). This reduced surface thrombogenicity after plaque ablation with either an erbium:YAG laser or a catalytic hot-tip catheter suggests that thermal modifications in the arterial surface ultrastructure or thermal denaturation of surface proteins, or both, may be responsible for reduced platelet adherence. These in vitro findings indicate that controlled thermal plaque ablation by catheter-based techniques may elicit endovascular responses that can reduce early thrombus formation during angioplasty procedures.