CONTEXT For more than 20 years, primary prevention of coronary heart disease has included strategies intended to improve overall serum lipid concentrations among youths. OBJECTIVE To examine trends in lipid concentrations among youths from 1988-1994 through 2007-2010. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of serum lipid concentrations among 16 116 youths aged 6 to 19 years who participated in the nationally representative National Health and Nutrition Examination Survey during 3 time periods: 1988-1994, 1999-2002, and 2007-2010. MAIN OUTCOME MEASURES Among all youths, mean serum total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C); and among adolescents only, low-density lipoprotein cholesterol (LDL-C) and geometric mean triglyceride levels. Trends in adverse lipid concentrations are reported for TC levels of 200 mg/dL and greater, non–HDL-C levels of 145 mg/dL and greater, HDL-C levels of less than 40 mg/dL, LDL-C levels of 130 mg/dL and greater, and triglyceride levels of 130 mg/dL and greater. RESULTS Among youths aged 6 to 19 years between 1988-1994 and 2007-2010, there was a decrease in mean TC (from 165 mg/dL 95% CI, 164-167 to 160 mg/dL 95% CI, 158-161; P < .001) and a decrease in the prevalence of elevated TC (from 11.3% 95% CI, 9.8%-12.7% to 8.1% 95% CI, 6.7%-9.5%; P = .002). Mean HDL-C significantly increased between 1988-1994 and 2007-2010, but the prevalence of low HDL-C did not change. Mean non–HDL-C and prevalence of elevated non–HDL-C both significantly decreased over the study period. In 2007-2010, 22% (95% CI, 20.3%-23.6%) of youths had either a low HDL-C level or high non–HDL-C, which was lower than the 27.2% (95% CI, 24.6%-29.7%) in 1988-1994 (P = .001). Among adolescents (aged 12-19 years) between 1988-1994 and 2007-2010, there was a decrease in mean LDL-C (from 95 mg/dL 95% CI, 92-98 to 90 mg/dL 95% CI, 88-91; P = .003) and a decrease in geometric mean triglycerides (from 82 mg/dL 95% CI, 78-86 to 73 mg/dL 95% CI, 70-76; P < .001). Prevalence of elevated LDL-C and triglycerides between 1988-1994 and 2007-2010 also significantly decreased. CONCLUSIONS Between 1988-1994 and 2007-2010, a favorable trend in serum lipid concentrations was observed among youths in the United States but almost 1 in 10 had elevated TC in 2007-2010.