<b><i>Background and Aims:</i></b> This ApoA5-1131C allele of rs662799 variant is related with a higher serum triglyceride levels, and it contributes to increase risk of cardiovascular disease. The aim of the present investigation was to evaluate single nucleotide polymorphism rs662799 in <i>APOA5</i> gene and its associations with cardiovascular risk factors, MS, and serum adipokine levels. <b><i>Methods:</i></b> The study involved a population of 1,002 Caucasian obese subjects. Measurements of body weight, waist circumference, fat mass, arterial blood pressure, blood glucose, C-reactive protein, insulin levels, insulin resistance (HOMA-IR), lipid profile, and adipokines levels were recorded. Genotype of <i>ApoA5</i> gene polymorphism (rs662799) and prevalence of metabolic syndrome (MS) were evaluated. <b><i>Results:</i></b> The distribution of the rs662799 polymorphism in this adult population (<i>n</i> = 1,002) was 88.3% (<i>n</i> = 885) (TT), 11.4% (<i>n</i> = 114) (TC), and 0.3% (<i>n</i> = 3) (CC). No significant differences were found between the 2 genotypes in the anthropometric data, MS, or blood pressure. Triglyceride levels were higher in C-allele carriers (delta total group: 19.7 ± 2.1 mg/dL: <i>p</i> = 0.02) than non C-allele carriers. HDL-cholesterol levels were lower in C-allele carriers (delta total group: −6.7 ± 1.1 mg/dL: <i>p</i> = 0.02) than non C-allele carriers. Adiponectin levels were lower in C-allele carriers (delta total group: −11.6 ± 1.0 mg/dL: <i>p</i> = 0.02) too. In C-allele carriers, logistic regression analysis showed an increased risk of hypertriglyceridemia (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.4, <i>p</i> = 0.001) and percentage of low-HDL-C (OR = 2.2, 95% CI = 1.3–3.7, <i>p</i> = 0.002) after adjusting by body mass index and age. <b><i>Conclusions:</i></b> C-allele carriers of rs662799 of <i>APOA5</i> gene showed high rates of low levels of HDL and hypertriglyceridemia, with differences in triglyceride, HDL cholesterol, and adiponectin levels in Caucasian obese subjects.