We aimed to evaluate the prevalence of familial hypercholesterolaemia (FH) in a subjectwith hypercholesterolaemia from two population-based cohorts in South Korea. A total of 283 subjects with total cholesterol levels of 290 mg/dL (7.5 mmol/L) or higherwere selected from the Namwon and Dong-gu Studies. We used next generation sequencing(NGS) to detect mutations in low-density lipoprotein receptors (LDLR), apolipoproteinB (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. We have confirmed 17 different mutations of the LDLR, APOB and PCSK9 in 23 subjects(8.1%). Eleven LDLR variants and one APOB variant have been previouslyreported. One LDLR and two PCSK9 rare variants were identified in the variants database,but not in the FH mutation database. Two novel LDLR variants were found,p.Leu680Val, and p.Thr734Phe. No LDLR, APOB or PCSK9 deletions nor insertionswere found. When the subjects were restricted to 110 subjects with a total cholesterol≥310 mg/dL, only 10 variants were found in the 10 subjects (9.1%). These results suggestthat given the low prevalence of FH mutations in subjects with high total cholesterollevels, NGS-based testing for a population-based approach to FH detection may notbe cost-effective.