Nonalcoholic fatty liver disease (NAFLD) has been consistently found to be associated with features of the metabolic syndrome (MS), a condition carrying a high risk of cardiovascular events. The present study aimed to determine whether, in children and adolescents, NAFLD is atherogenic beyond its association with MS and its components. We assessed both flowmediated dilation of the brachial artery (FMD) and carotid intima-media thickness (cIMT), along with lipid profile, glucose, insulin, insulin resistance, and high-sensitivity C-reactive protein (CRPHS), in 250 obese children, 100 with and 150 without NAFLD, and 150 healthy normal-weight children. NAFLD was diagnosed by ultrasound examination and persistently elevated alanine aminotransferase, after exclusion of infectious and metabolic disorders. Compared to controls and children without liver involvement, those with ultrasounddiagnosed NAFLD (and elevated alanine aminotransferase) demonstrated significantly impaired FMD and increased cIMT. Patients with NAFLD had more features of MS and elevated CRPHS levels. In addition, percent FMD was remarkably reduced, whereas cIMT was increased in obese children with MS compared to those without MS. Using logistic regression analysis, the presence of NAFLD was found to be an independent predictor of low percent FMD (odds ratio, 2.25 [95% confidence interval, 1.29 to 3.92]; P 5 0.004) as well as of increased cIMT (1.98 [1.16 to 3.36]; P 5 0.031), after adjustment for age, gender, Tanner stage, and presence of MS. When we analyzed the relations between cIMT and measures of FMD in patients with NAFLD, the disease was associated with increased cIMT in children with impaired FMD status. Conclusion: The presence of liver disease entails more severe functional and anatomic changes in the arterial wall. Its detection may help identify individuals with increased cardiometabolic risk. (HEPATOLOGY 2010;52:1643-1651) O ver the last two decades the rise in the prevalence rates of overweight and obesity may explain the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of liver disease in pediatric populations worldwide. 1 NAFLD comprises a disease spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), progressive to cirrhosis. NAFLD is presently considered a hepatic manifestation of the metabolic syndrome (MS), with insulin resistance (IR) as the main pathogenetic mechanism. 2 Because of the underlying metabolic disorder, NAFLD patients are expected to have a higher risk of vascular and coronary heart disease as well. Indeed, it has been reported that subjects with fatty liver have elevated levels of plasma biomarkers of inflammation, impaired endothelial function, and early carotid changes. 3,4 Carotid intima-media thickness (cIMT) and brachial flow-mediated dilation (FMD) as assessed noninvasively by ultrasound are preclinical