To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Cross-sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5-17years). Metabolic syndrome was defined by≥3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high-density lipoproteins; (4) fasting glucose ≥100mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80mmHg in adolescents. High serum uric acid was defined as serum UA value≥75th percentile adjusted for sex. Fatty liver disease was determined by echography. The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA+MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p<0.0001). The ORs for the categorical variables were 1.33 (1.06-1.68) for MetS (p=0.02), 3.19 (2.51-4.05) for HUA (p<0.0001) and 3.72 (2.65-5.21) for HUA+MetS (p<0.0001), versus the reference category regardless of the body mass index. HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study.