A standard (“core”) implementation of American College of Cardiology/American Heart Association 2013 lipid guidelines (based on 10-year risk) dramatically increases the statin-eligible population in older Americans, raising controversy in the cardiovascular community. The guidelines also endorse a more “comprehensive” risk approach based in part on lifetime risk. The impact of this broader approach on statin eligibility remains unclear. We studied the impact of 2 different implementations of the new guidelines (“core” and “comprehensive”) using the National Health and Nutrition Examination Survey. Although “core” guidelines led to 72.0 million subjects qualifying for statin therapy, the broader “comprehensive” application led to nearly a twofold greater estimate for statin-eligible subjects (121.2 million), with the greatest impact among those aged 21 to 45 years. Subjects indicated for statin therapy under comprehensive guidelines had a greater burden of cardiovascular risk factors and a higher lifetime risk of cardiovascular disease than those not indicated for statins. In particular, men aged 21 to 45 years had a 3.13-fold increased odds of being eligible for statin therapy only under the “comprehensive” guidelines (vs standard “core” guidelines; 95% confidence interval 2.82 to 3.47, p <0.0001). There were no racial differences. In conclusion, the “comprehensive” approach to statin eligibility espoused by the American College of Cardiology/American Heart Association 2013 guidelines would increase the statin-eligible population to over 120 million Americans, particularly targeting younger men with high–risk factor burden.