FOXA3 is a transcription factor involved in the macrophage cholesterol efflux and macrophage reverse cholesterol transport reducing the atherosclerotic lesions. Thus, the present study aimed to establish if the FOXA3 polymorphisms are associated with subclinical atherosclerosis (SA) and cardiometabolic parameters. Two FOXA3 polymorphisms (rs10410870 and rs10412574) were determined in 386 individuals with SA and 1070 controls. No association with SA was observed. The rs10410870 polymorphism was associated with a low risk of having total cholesterol >200 mg/dL, non-HDL-cholesterol > 160 mg/dL, and a high risk of having LDL pattern B and insulin resistance adipose tissue in individuals with SA, and with a high risk of having interleukin 10 <p25 and magnesium deficiency in controls. The rs10412574 polymorphism was associated with a low risk of insulin resistance of the adipose tissue and a high risk of aspartate aminotransferase >p75 in individuals with SA, and with a low risk of LDL pattern B and a high risk of a magnesium deficiency in controls. Independent analysis in 846 individuals showed that the rs10410870 polymorphism was associated with a high risk of aortic valve calcification. In summary, FOXA3 polymorphisms were not associated with SA; however, they were associated with cardiometabolic parameters in individuals with and without SA.