The vegan diet excludes animal-derived product consumption and has been linked with cardiovascular benefits. The objective of the present comparative pilot study was to analyze dietary lipid intake, evaluate the conventional clinical lipid profile, extract fatty acids from triglycerides' molecules among Mexican individuals with prolonged exposure to a vegan diet (≥ 3 years), and compare these outcomes with omnivore controls. A case-control and cross-sectional comparative pilot study was performed between 2016 and 2017. Vegans were paired in a 1:1 ratio with omnivores from Merida, Mexico. A 144-item Semi-Quantitative Food Frequency Questionnaire was conducted to evaluate eating patterns. Serum fatty acids were determined from total blood with a gas chromatography assay. Lower total cholesterol, stearic, arachidonic, and trans fatty acids intake (p<0.001, 0.014, <0.001, 0.009 respectively), but higher consumption of lauric acid were observed in the vegan group (p= 0.007). Vegan-diet consumers also presented greater triglycerides concentrations (p= 0.049); however, when analyzing fatty acids, we identified lower levels of stearic, oleic, linoleic, and arachidonic acids (p= 0.002, 0.030, 0.015, 0.008, respectively). Following a vegan diet for more than three years generate modifications in serum concentrations of saturated and polyunsaturated ω-6 fatty acids, which could lower inflammatory markers' biosynthesis. Potential benefits regarding cardiovascular risk may be assumed in favor of vegan individuals.