Apolipoprotein (Apo) A-II is an apolipoprotein with an unknown role in lipid metabolism. It has been suggested that the presence of the less frequent allele of a single nucleotide polymorphism (Apo A-II -265T/C, rs5082) reduces the transcription rate of Apo A-II and enhances VLDL postprandial clearance in middle-aged men. To further investigate the role of Apo A-II -265T/C on lipid metabolism, we studied 88 normolipidemic young men. The participants were given a fatty meal containing 1 g fat and 7 mg cholesterol/kg weight and capsules containing 60,000 IU vitamin A (retinyl palmitate, 15.15 mg RE) per square meter body surface area. Postprandial lipemia was assessed during the 11 h following the meal. Total cholesterol (Chol) and triacylglycerols (TG) in plasma and TG-rich lipoproteins (TRL) (large TRL and small TRL) were measured, as well as HDL, Apo A-I, Apo B, Apo B-48, and Apo B-100. Postprandial responses were higher in the TT group than in carriers of the minor allele (CC/TC) for total TG in plasma (21.37% of change of area under curve, P = 0.014), large TRL-TG (24.75% change, P = 0.017) and small TRL-Chol (26.63% change, P = 0.003). Our work shows that carriers of the minor allele for Apo A-II -265T/C (CC/TC) have a lower postprandial response compared with TT homozygotes. This finding may partially explain the role of Apo A-II in lipid metabolism and can identify a population with a decreased risk of cardiovascular disease, as corresponds to the lower level of postprandial hypertriglyceridemia.