OBJECTIVES: This study sought to assess whether oxidized lipids are released downstream from obstructive plaques after percutaneous coronary and peripheral interventions using distal protection devices. BACKGROUND: Oxidation of lipoproteins generates multiple bioactive oxidized lipids that affect atherothrombosis and endothelial function. Direct evidence of their role during therapeutic procedures, which may result in no-reflow phenomenon, myocardial infarction, and stroke, is lacking. METHODS: The presence of specific oxidized lipids was assessed in embolized material captured by distal protection filter devices during uncomplicated saphenous vein graft, carotid, renal, and superficial femoral artery interventions. The presence of oxidized phospholipids (OxPL) and oxidized cholesteryl esters (OxCE) was evaluated in 24 filters using liquid chromatography, tandem mass spectrometry, enzyme-linked immunosorbent assays, and immunostaining. RESULTS: Phosphatidylcholine-containing OxPL, including (1-palmitoyl-2-[9-oxo-nonanoyl] PC), representing a major phosphatidylcholine-OxPL molecule quantitated within plaque material, [1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphocholine], and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, were identified in the extracted lipid portion from all vascular beds. Several species of OxCE, such as keto, hydroperoxide, hydroxy, and epoxy cholesteryl ester derivatives from cholesteryl linoleate and cholesteryl arachidonate, were also present. The presence of OxPL was confirmed using enzyme-linked immunoassays and immunohistochemistry of captured material. CONCLUSIONS: This study documents the direct release and capture of OxPL and OxCE during percutaneous interventions from multiple arterial beds in humans. Entrance of bioactive oxidized lipids into the microcirculation may mediate adverse clinical outcomes during therapeutic procedures.