BACKGROUND: Diet, smoking and physical activity are important modifiable lifestyle factors that can influence body weight and fat accumulation. We assessed the relationship between lifestyle and obesity risk in a baseline analysis of the PREDIMED study, a randomized dietary primary prevention trial conducted in Spain. METHODS: 7000 subjects at high cardiovascular risk were assessed cross-sectionally. A healthy lifestyle pattern (HLP) was determined using a score including: adherence to the Mediterranean diet, moderate alcohol consumption, expending ≥200 kcal/day in leisure-time physical activity, and non-smoking. RESULTS: Inverse linear trends were observed between the HLP-score and body-mass-index (BMI) or waist circumference (p<0.001). The BMI and waist circumference of participants with a HLP-score=4 were, respectively, 1.3 kg/m(2) (95% CI: 0.9 to 1.7) and 4.3 cm (3.1 to 5.4) lower than those of subjects with an HLP≤1. The odds ratios of general obesity and abdominal obesity for an HLP score of 4 compared to an HPL score≤1 were 0.50 (0.42 to 0.60) and 0.51 (0.41 to 0.62), respectively. CONCLUSION: A combination of four healthy lifestyle behaviors was associated with a lower prevalence of general obesity and abdominal obesity in Mediterranean elderly subjects at high cardiovascular risk.