Introduction: Genetic load may indirectly influence on cardiovascular risk. This work aimed to analyze the influence of polymorphisms (APOA5 C56G‑ Ser19Trp, Prothrombin‑ G20210A, F5 Arg506Gln, MTHFR‑ C677T, LIPC‑ C‑ 514T, LPA‑ I4300M, PPAR_ALPHA‑ L162V, APOA5‑ 1131T > C, APOE‑ APOE2/3/4, and APOE‑ APOE2, 3, 4) in plasma triglyceride (TG) levels of patients ingesting plant sterols. Materials and Methods: Double‑ blind, crossover, controlled clinical trial was performed in 45 individuals (25 women). About 2. 24 g sterols in milk and placebo milk were ingested daily during 3 weeks each, separated by a 2‑ week washout period. Blood draws and saliva genomic DNA was extracted. Results: APOA5‑ C56G‑ Ser19Trp, MTHFR‑ C677T, and PPAR_ALPHA‑ L162V greatly benefit from sterols intake. APOA5‑ C56G‑ Ser19Trp GG homozygous carriers lowered their TGs more than CG heterozygote carriers (P = 0. 003). TT homozygous carriers of gene LIPC C‑ 514T experienced an increase of TGs. Conclusions: Further studies are needed to establish which genotype combinations is the most protective against hypertriglyceridemia.