SUA is associated with cardiovascular disease and cardiovascular disease risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes mellitus, preeclampsia, and hypertension. A cross-sectional study was carried out among 11219 adolescents 12 to 18 years of age examined in the 2001-2018 National health and Nutrition Examination Survey. We examined the association between SUA and CVD risk factors. The overall mean SUA level was 5.00±1.24mg/dl. Restricted cubic spline analysis results revealed SUA was inversely associated with HDL-C and SPISE and positively associated with TC, TG, LDL-C, nonHDL-C, insulin, SBP and DBP after full adjustment. Multiple logistic analyses showed SUA level was independently associated with high TC, high TG, high nonHDL-C and low HDL-C (all p<0.05). Furthermore, females in the highest quartile of SUA had significantly higher odds for elevated BP (OR = 2.38, 95%CI:1.02-5.54, P<0.05) and high TC (OR = 2.22, 95%CI: 1.49-3.30, P<0.001), which not observed in males. Increased levels of SUA were associated with increased odds of various cardiovascular risk factors in American adolescents, especially females.