Background <p>The rs688 polymorphism in the LDLR gene has been linked to lipid profile alterations, yet its impact in patients at high to very high cardiovascular risk remains unclear.</p> Objectives <p>To investigate the association between the LDLR rs688 polymorphism and dyslipidemia in high to very high cardiovascular risk patients.</p> Methods <p>This cross-sectional study included patients classified as high or very high cardiovascular risk and matched controls at Can Tho University of Medicine and Pharmacy Hospital. Blood lipid profiles and LDLR rs688 genotyping were assessed using Realtime-PCR.</p> Results <p>Among 80 patients (mean age 62.36 ± 10.49 years; 35.0% male), CT and TT genotypes were more frequent compared to controls (37.5% vs. 30.6%, and 15.0% vs. 3.8%, respectively). The T allele was also more prevalent (33.8% vs. 19.1%). Dyslipidemia was present in 68.8% of patients. T allele carriers had higher dyslipidemia rates (90.7% vs. 57.5%), higher LDLc (5.42 ± 1.51 mmol/L vs. 3.19 ± 1.37 mmol/L), and lower HDLc (0.70 ± 0.25 mmol/L vs. 1.03 ± 0.32 mmol/L) compared to C allele carriers. Multivariate analysis identified the T allele (OR = 14.18) and diabetes mellitus (OR = 4.85) as independent predictors of dyslipidemia.</p> Conclusion <p>The LDLR rs688 T allele and diabetes mellitus independently increases dyslipidemia risk among patients at high to very high cardiovascular risk.</p>