Significance: Research has suggested that 25% of the adult population twenty years of age or older have blood cholesterol levels that are elevated. Therefore, establishing specific guidelines for cholesterol levels is important to community health. The purpose of this study was to examine differences in risk stratification when using ATP-III National Cholesterol Education Program guidelines and the emerging risk designation of cholesterol concentration and size among at-risk participants. Design: Lipid profiles were conducted on 541 at-risk (based on previous screenings) participants who consented to give blood for research purposes. Lipid profiles were measured using gel electrophoresis and their particle size and concentration measured using Nuclear Magnetic Resonance (NMR) spectroscopy. Risk stratification was compared between each lipid measure for group analysis. Statistical analysis included descriptive statistics to compare the differences in the number of participants considered at-risk based on ATP-III guidelines and those at-risk using measurements of particle size and number. Correlation between plasma LDL and particle number was assessed by calculating Pearson's correlation coefficients. Distribution normality was calculated by a one sample Kolmogorov-Smirnov test for normality. Results: Pearson's correlation coefficients revealed a strong correlation between LDL cholesterol and LDL concentration (r2=.802, p=.0001) and a significant inverse correlation between LDL concentration and size (r2= -.374, p =.0001). A weak non-significant correlation existed between LDL cholesterol and LDL size (r2= .041, p=.649). A one-sample Kolmogorov-Smirnov test for normality was calculated for LDL with a p-value of 0.654 revealing insufficient evidence that the distribution is not normally distributed. Twenty-seven participants (5.0%) of the original cohort of 541 were considered at-risk when using the ATP-III guidelines for LDL cholesterol. Using the same patient pool, 86 participants (15.90%) were considered at risk when using large LDL-Phenotype B. Using LDL-Phenotype B helped to identify an additional 10.09% of participants who could be classified as at-risk. The findings suggest a “disconnect” between traditional lipid measures and cholesterol size when using ATP-III guidelines for risk stratification. The cholesterol risk designation variances between risk stratification guidelines, as illustrated within this participant pool, reveal the complex interactions responsible for the development of atherosclerosis. The additional participants considered at-risk using NMR technology may help to identify more participants at need for intervention and treatment and when combined with dietary and exercise behavior change, can improve the risk profile and possibly reduced the number of people having cardiovascular disease. Keyword(s): disease prevention/wellness, measurement/evaluation, research