Abstract The influence of blood medium on tissue ablation by a pulsed dye laser and its selectivity for atheroma were investigated. The role of shock waves on tissue ablation was also evaluated. Normal and atherosclerotic human aortas were irradiated by a 480 nm pulsed dye laser activated at 5 Hz. The laser was coupled with a single 0.2 mm fiber (Uni-gulde) (40 mjoules/pulse) or a multifiber catheter (14× 150 μm) (100 mjoules/pulse). Shock waves were measured using a fluid-filled catheter connected to a strain gauge manometer. With the Uni-guide, pulse-dye lasing resulted in greater ablation of atheroma in blood (11.6 × 10 −3 mm 3/joule, p <0.001 versus atheroma measured in saline and normal tissue in blood) followed by normal tissue in blood (2.5 × 10 −3mm 3/joule), atheroma in saline (1.71 × 10 −3mm 3/joule, p < 0.05 versus normal tissue in saline), and normal tissue in saline (0.54 × 10 −3 mm 3/joule). With the multifiber catheter, laser ablation was the greatest in atheroma in blood (0.55 ± 0.26 mm 3/joule p < 0.001 versus atheroma in saline and normal tissue in blood), followed by normal tissue in blood (0.27 ± 0.12 mm 3/joule), atheroma in saline (0.14 ± 0.15 mm 3/joule, p < 0.001 versus normal tissue in saline), and normal tissue in saline (0 mm 3/joule). The ablation efficlency of the muitifiber catheter was greater than that of the Uni-gulde ( p < 0.0001) At 100 mjoules/pulse, shock waves were the greatest for atheroma in blood (1.47 mm Hg, p < .005 versus normal tissue in blood, p < 0.001 versus atheroma in saline), followed by 0.28 mm Hg in normal tissue in blood, 0.09 mm Hg for atheroma in saline, and 0 mm Hg for normal tissue in saline. The magnitude of shock waves was correlated with ablation officiency ( r = 0.64). In the same specimens ( n = 5), shock waves were 0 at 25 mjoules/pulse, 0.56 mm Hg/pulse at 50 mjoules/pulse, and 1.45 mm Hg at 100 mjoules/pulse ( p < 0.05 versus 50 mjoules/pulse). Heavily calcifled plaques were also ablated with the laser. The craters created in blood occasionally showed irregular edges; however, no extensive thermal injury was observed. In conclusion, we determined: (1) pulsed dye laser at 480 nm selectively ablates atheromatous tissue; (2) blood medium enhances the ablation efficiency of pulsed-dye laser; (3) ablation efficiency is correlated with the magnitude of shock waves; (4) calcified plaques can be ablated by a pulsed-dye laser; and (5) a multifiber catheter is more sultable for laser angloplasty than the Uni-guide.