This multicenter, randomized, controlled, parallel trial compared the effect of 2 types of traditional Mediterranean diets (TMDs), one supplemented with virgin olive oil (VOO) and the other with mixed nuts, with that of a low-fat diet on markers of lipid oxidative damage and endogenous antioxidant status. Participants included 372 subjects at high cardiovascular risk (210 women and 162 men) aged 55 to 80 years. The TMD participants received nutritional education and either free VOO for all the family (1 L/wk) or free nuts (30 g/d). After the 3-month interventions, mean (95% confidence interval [CI]) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + VOO (−10.6 U/L [−14.2 to −6.1 U/L]) and in the TMD + nuts (−7.3 U/L [−11.2 to −3.3 U/L]) groups, without changes in the low-fat group (−2.9 U/L [−7.3 to 1.5 U/L]). Change in oxidized LDL level in the TMD + VOO group reached significance vs that of the low-fat group (P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. Thus, individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in their cellular lipid level and LDL oxidation.