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Although the Friedewald method has been used as the clinical standard to estimate low-density lipoprotein cholesterol (LDL-C) levels, a novel method with better accuracy was suggested and is now being adopted in real practice. We investigated the effect of this novel method on determining the eligibility for statin treatment for primary prevention in the United States.In this cross-sectional study, we determined the discordance in the statin-eligible population for primary prevention according to the 2 different LDL-C estimating methods based on the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Using data from the National Health and Nutrition Examination Survey 2005–2014, we included 5302 nationally representative US adults aged between 40 and 75 years without history of atherosclerotic cardiovascular disease (ASCVD). Sampling weights were used in all statistical analyses to account for complex sampling design and nonresponse.If the Friedewald method is replaced by the novel method for analysis of the fasting samples, 0.2% (95% confidence interval [CI], 0.0–0.8) and 0.4% (95% CI, 0.3–0.6) of the population would no longer be eligible or would become newly eligible for statin treatment, respectively. Among the individuals with a TG level ≥150 mg/dL and LDL-C level estimated using the Friedewald method <70 mg/dL, 11.6% (95% CI, 4.0–29.3) would become newly eligible for the statin treatment when using the novel method.The use of the novel method for estimating LDL-C instead of the Friedewald method would be associated with a small net increase in statin eligible/needed US adults for primary prevention based on the 2013 ACC/AHA guidelines. Reassessment of individuals’ statin eligibility using the novel method may be beneficial, particularly when their TG level is 150 mg/dL or higher and LDL-CF level is lower than 70 mg/dL.