AIMS The aims of this study were to estimate the prevalence of low high-density lipoprotein cholesterol (HDL-C) in US adults, assess the association between low HDL-C levels and clinical characteristics, and quantify the utilization of dyslipidemic agents as it relates to the distribution of HDL-C. METHODS We analyzed a sample of 4129 adults (>20 years) who underwent fasting blood evaluations in the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Sex-specific crude and adjusted logistic models were developed to evaluate the association between individual characteristics and low HDL-C, in which low HDL-C was defined as less than 40 mg/dl for men and less than 50 mg/dl for women. RESULTS Approximately 24% of men and 27% of women had low HDL-C levels. Factors most strongly associated with low HDL-C levels for men included being obese [odds ratio (OR) = 3.27, 95% confidence interval (CI): 1.98-5.40], having elevated triglyceride levels (>200 mg/dl: OR = 8.17, 95% CI: 5.54-12.03) and having apolipoprotein B levels more than 117 mg/dl (OR = 5.99, 95% CI: 2.74-13.13). The same factors were associated with low HDL-C levels among women: being obese (OR = 2.89, 95% CI: 1.78-4.71), having elevated triglyceride levels (>200 mg/dl: OR = 13.35, 95% CI: 7.49-23.77) and having apolipoprotein B levels more than 117 mg/dl (OR = 5.88, 95% CI: 2.29-15.11). Approximately 82% of men and 79% of women with low HDL-C levels reported not using any dyslipidemic medication. CONCLUSION Although having low HDL-C was common among US adults, few reported taking a dyslipidemic agent. Our study also confirmed some of the known risk factors associated with low HDL-C levels in the general US population.