BACKGROUND: Familial hypercholesterolemia (FH) is an inherited condition that likely affects 1 in 300 people often requiring pharmacologic intervention in childhood. OBJECTIVES: We hypothesized that current strategies for pediatric lipid screening fail to detect and treat most FH, but data analysis may suggest specific methods to improve outcomes. METHODS: We retrospectively searched 392,129 patient records of 11-17-year-olds in Kaiser Permanente Southern California for data related to recommended universal pediatric lipid screening. We categorized subjects as Probable or Possible FH and evaluated FH pharmacotherapy status. RESULTS: 37% of the population received lipid screening with 0.13% (1 in 769) having Probable or Possible FH. Results at each step of the process showed progressive decreases in detection and treatment. We characterized 1 in 3448 subjects as Probable FH which is only 8.7% of cases expected from the prevalence of FH in the population. 45% of Probable FH cases received ongoing pharmacotherapy which is 1 in 7688 of the cohort (3.9% of expected cases). One major correctable reason for this drop-off was using obesity to target screening and treatment decisions rather than following the recommended universal screening. We found a strong association of obesity with screening (risk ratio (RR) 2.74 [confidence interval (CI) 2.71-2.76]), but not with FH (RR 0.72, CI 0.47-1.10). CONCLUSION: This current universal lipid screening strategy, likely typical of US practice, fails to detect and treat the supermajority of FH cases, increasing risk for adult coronary artery disease. To address the specific deficiencies we observed, we suggest improvements to detect and treat FH.