BACKGROUND AND AIMS:non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries. This study aimed to investigate putative risk factors differentially related with NAFLD in obese males and females diagnosed with metabolic syndrome (MetS), stratified using the non-invasive hepatic steatosis index (HSI). METHODS AND RESULTS:a cross-sectional analysis of the PREDIMED Plus study was performed of 278 participants with MetS (141 males and 137 females) of the Navarra-Nutrition node. Subjects were categorized by HSI tertiles and gender. Baseline clinical, biochemical variants and adherence to a Mediterranean diet and physical activity were evaluated. RESULTS:multivariate analyses showed that females had 4.54 more units of HSI (95% CI: 3.41 to 5.68) than males. Both sexes showed increased levels of triglycerides, TG/HDL cholesterol ratio and triglyceride glucose index across the HSI tertiles. Physical activity exhibited a negative statistical association with HSI (males: r = -0.19, p = 0.025; females: r = -0.18, p = 0.031). The amount of visceral fat showed a positive association with HSI in both sexes (males: r = 0.64, p < 0.001; females: r = 0.46, p < 0.001). Adherence to the Mediterranean diet was lower in those subjects with higher HSI values (males: r = -0.18, p = 0.032; females r= -0.19, p = 0.027). CONCLUSION:females had a poor liver status, suggesting gender differences related to NAFLD. Adherence to a Mediterranean diet and physical activity were associated with beneficial effects on cardiovascular disease features. Thus, reducing the risk of hepatic steatosis in subjects with MetS and obesity.