The American Heart Association (AHA) and World Health Organization (WHO) have recommended restricting calories from added sugars at lower levels than the Institute of Medicine (IOM) recommendations, which are incorporated in the Dietary Guidelines for Americans 2010 (DGAs 2010). Sucrose (SUC) and high fructose corn syrup (HFCS) have been singled out for particular concern, because of their fructose content, which has been specifically implicated for its atherogenic potential and possible role in elevating blood pressure through uric acid-mediated endothelial dysfunction. This study explored the effects when these sugars are consumed at typical population levels up to the 90th percentile population consumption level for fructose. Three hundred fifty five overweight or obese individuals aged 20-60 years old were placed on a eucaloric diet for 10 weeks, which incorporated SUC- or HFCS-sweetened, low-fat milk at 8%, 18% or 30% of calories. There was a slight change in body weight in the entire cohort (169.1 ± 30.6 vs. 171.6 ± 31.8 lbs, p < 0.01), a decrease in HDL (52.9 ± 12.2 vs. 52.0 ± 13.9 mg/dL, p < 0.05) and an increase in triglycerides (104.1 ± 51.8 vs. 114.1 ± 64.7 mg/dL, p < 0.001). However, total cholesterol (183.5 ± 42.8 vs. 184.4 mg/dL, p > 0.05), LDL (110.3 ± 32.0 vs. 110.5 ± 38.9 mg/dL, p > 0.05), SBP (109.4 ± 10.9 vs. 108.3 ± 10.9 mmHg, p > 0.05) and DBP (72.1 ± 8.0 vs. 71.3 ± 8.0 mmHg, p > 0.05) were all unchanged. In no instance did the amount or type of sugar consumed affect the response to the intervention (interaction p > 0.05). These data suggest that: (1) when consumed as part of a normal diet, common fructose-containing sugars do not raise blood pressure, even when consumed at the 90th percentile population consumption level for fructose (five times the upper level recommended by the AHA and three times the upper level recommended by WHO); (2) changes in the lipid profile are mixed, but modest.