BACKGROUND:The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors. OBJECTIVE:To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk. DESIGN:Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevención con Dieta Mediterránea [PREDIMED] Study). SETTING:Primary care centers affiliated with 10 teaching hospitals. PARTICIPANTS:772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. INTERVENTIONS:Participants were assigned to a low-fat diet (n = 257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n = 258). The authors evaluated outcome changes at 3 months. MEASUREMENTS:Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules. RESULTS:The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were -0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L), respectively, for plasma glucose levels; -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg), respectively, for systolic blood pressure; and -0.38 (CI, -0.55 to -0.22) and - 0.26 (CI, -0.42 to -0.10), respectively, for the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet. LIMITATIONS:This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets. CONCLUSION:Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.