Data from National Health and Nutrition Examination Survey (NHANES) II (1976 to 1980), NHANES III (1988 to 1994), and NHANES 1999 to 2006 were examined to assess trends in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides (TGs), lipid-lowering medication use, and obesity. Age-adjusted decreases in TC (210 to 200 mg/dl) and LDL cholesterol (134 to 119 mg/dl) were observed. Those with high TC showed a decrease of 9% from NHANES II to NHANES 1999 to 2006, whereas those with LDL cholesterol ≥160 mg/dl showed a decrease of 8%. A significant increase in mean high-density lipoprotein cholesterol was observed (50 to 53 mg/dl, p <0.001), most likely due to changes in methods. Those with TG levels ≥150 mg/dl showed a decrease from NHANES II to NHANES III from 30% to 27% but then an increase from NHANES III to NHANES 1999 to 2006 from 27% to 33%. Since NHANES III, mean TG levels have increased 12% from 130 to 146 mg/dl. In the 2 most recent surveys, self-reported "high cholesterol" increased from 17% to 27%, and self-reported lipid medication use by those with high cholesterol increased from 16% to 38%. Mean body mass index increased from 26 to 29 kg/m(2), and prevalence of obesity doubled and was significantly associated with increased TG. In conclusion, recent favorable trends in TC and LDL cholesterol are likely due to increased awareness of high cholesterol and the greater use of lipid-lowering drugs. However, countertrends in obesity and TG levels, if continued, will likely have a negative impact on cardiovascular disease in the future.