Simultaneously produced superoxide/nitric oxide radicals (O ⋅− 2/NO ⋅) could form peroxynitrite (OONO −) which has been found to cause atherogenic, i.e. oxidative modification of LDL. Aromatic hydroxylation and nitration of the aspirin metabolite salicylate by OONO − has been reported. Therefore we tested if salicylate may be able to protect LDL from oxidation by O ⋅− 2/NO ⋅ by scavenging the OONO − reactive decomposition products. When LDL was exposed to simultaneously produced O ⋅− 2/NO ⋅ using the sydnonimine SIN-1, salicylate exerted an inhibitory effect on LDL oxidation as measured by TBARS and lipid hydroperoxide formation and alteration in electrophoretic mobility of LDL. The cytotoxic effect of SIN-1 pre-oxidised LDL to endothelial cells was also diminished when salicylate was present during SIN-1 treatment of LDL. Spectrophotometric analysis revealed that salicylate was converted to dihydroxybenzoic acid (DHBA) derivatives in the presence of SIN-1. 2,3- and 2,5-DHBA were even more effective to protect LDL from oxidation by O ⋅− 2/NO ⋅. Because O ⋅− 2/NO ⋅ can occur in vivo, the results may indicate that salicylate could act as an efficacious inhibitor of O ⋅− 2/NO ⋅ initiated atherogenic LDL modification, thus further supporting the rationale of aspirin medication regarding cardiovascular diseases.