OBJECTIVES: To investigate the usefulness of National Health and Nutrition Examination Survey (NHANES) data for exposure estimates. To illustrate its utility, the relationship between biomarkers of exposure (serum cotinine) and cardiovascular disease (WBC, Apo lipoprotein, C-reactive protein, HDL, LDL, total cholesterol) among current, past, and non smokers was examined using NHANES 2007-2010. METHODS: Data were obtained from NHANES 2007 to 2010. The study sample had 11, 960 respondents who were 21 years and above, answered questions on cigarette smoking and had complete laboratory values for their biomarkers measurement. The population was categorized as current, past, and non smokers. The exposure variable was serum cotinine concentration and the outcome variables were serum levels of the biomarkers listed above. Weighted survey linear regression was used to estimate the association between cotinine concentration and biomarkers levels. We also tested the models for different levels of covariates; age, sex, race and body mass index (BMI). RESULTS: The levels of WBC (F-value: 38.78; P-value: <.0001) and HDL (F-value: 26.43; P-value: <.0001) showed higher association with cotinine levels than rest of the biomarkers. The R2for the models ranged from 0.039-0.261. Higher levels of WBC and lower levels of HDL were observed among current smokers relative to past and non smokers. BMI showed a high association with most of the biomarkers. The odds of lower HDL were significantly higher for 21-35 years age group relative to the >65 years age group. Non-Hispanic blacks had a significantly lower HDL than non-Hispanic whites. Females had significantly higher HDL than males. These results were consistent with that reported in the literature. CONCLUSIONS: A statistically significant association was observed between the biomarker of exposure (serum cotinine) and WBC and HDL cholesterol. There were also significant differences in the association within the different covariate levels.