Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is regarded as the hepatic manifestation of the metabolic syndrome. In adults, NAFLD is a determinant of arterial stiffness and cardiovascular risk, independent of the metabolic syndrome. Our aim was to ascertain if NAFLD is associated with arterial stiffness, independent of cardiometabolic factors in a population-based cohort of adolescents. The 17-year-olds (n 5 964) from an Australian birth cohort had measures of anthropometry, blood pressure, fasting insulin, glucose, lipids, and NAFLD by ultrasound. Two-step cluster analysis identified youth at high metabolic risk. Measures of arterial stiffness (pulse wave velocity [PWV] and augmentation index corrected for heart rate [AI@75]) were obtained using applanation tonometry. The overall prevalence of NAFLD was 13.3%. The "high risk" metabolic cluster at age 17 years included 16% males and 19% females. Compared to "low risk," the "high risk" cluster participants had greater waist circumference, triglycerides, insulin, systolic blood pressure, and lower high-density lipoprotein (HDL) cholesterol (all P < 0.0001). Those who had NAFLD but were not in the "high risk" metabolic cluster did not have increased PWV or AI@75. However, males and females who had NAFLD in the presence of the metabolic cluster had greater PWV (b 5 0.20, 95% confidence interval [CI] 0.01 to 0.38, P 5 0.037). Males who had NAFLD in the presence of the metabolic cluster had greater AI@75 (b 5 6.3, 95% CI 1.9 to 10.7, P 5 0.005). Conclusion: NAFLD is only associated with increased arterial stiffness in the presence of the "high risk" metabolic cluster. This suggests that arterial stiffness related to the presence of NAFLD is predicated on the presence of an adverse metabolic profile in adolescents. (HEPATOLOGY 2013;58:1306-1314 N onalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition worldwide, affecting between 15%-30% of adults and 13%-18% of adolescents.1,2 The development of NAFLD is intimately related to key components of the metabolic syndrome, namely, central obesity, disturbed lipid metabolism, and insulin resistance. Thus, NAFLD has been considered the hepatic component of the metabolic syndrome.3 As the metabolic syndrome is a cluster of factors that predict cardiovascular disease (CVD), it is not surprising that CVD is the leading cause of death in patients with NAFLD, accounting for 30% of all deaths. 4,5 In contrast, only a small proportion of subjects with NAFLD develop cirrhosis or die from complications of their liver disease.Abbreviations: AI@75, augmentation index corrected for heart rate; AIx, aortic augmentation index; CVD, cardiovascular disease; HOMA-IR, homeostasis model for insulin resistance; hsCRP, high sensitivity C-reactive protein; NAFLD, nonalcoholic fatty liver disease; PWC 170 , physical work capacity at a heart rate of 170 beats per minute; PWV, pulse wave velocity.From the