High-density lipoprotein (HDL) cholesterol levels are associated with decreased risk of coronary artery disease. Several genome-wide association studies (GWAS) for HDL cholesterol levels have implicated Lipoprotein lipase (LPL) as possibly being causal. Herein, the association between single nucleotide polymorphism (SNP) rs10503669 in the LPL gene and HDL cholesterol levels and triglyceride levels was tested in the Korean population. A total of 994 subjects from Seoul City were included in a replication study with LPL SNP rs10503669. SNP rs10503669 in the LPL gene was associated with mean HDL cholesterol levels (effect per allele 3.13 mg/dL, P<0.0001) and triglyceride levels (effect per allele -18.0 mg/dL, P=0.0026). Subjects with the CA/AA genotype had a 0.42-fold (range 0.23~0.77-fold) lower risk of having abnormal HDL cholesterol levels (<40 mg/dL) than subjects with the CC genotype. When analyzed by gender, the association of LPL was stronger in men than in women. This study clearly demonstrates that genetic variants in LPL influence HDL cholesterol levels and triglyceride levels in Korean adults.