BACKGROUND: The response to dietary fat plays a key role in metabolic health. Although this can vary widely between individuals, variation within an individual and the associated contribution of phenotypic and genotypic factors to this variation are less defined.Objectives: The objectives were to quantify within-person variation in triacylglycerol response by means of a novel variation score (S(v)) and to explore the phenotypic and genotypic factors associated with this score. DESIGN: Two consecutive 5-h oral-lipid-tolerance tests (OLTTs) were conducted in 51 healthy adults aged 18-60 y with a BMI (in kg/m(2)) of 18.5 to 49.8. Detailed body composition, physical function, biochemistry, and genotype data were gathered. RESULTS: The postprandial triacylglycerol response profile did not differ (P = 0.64) across OLTTs for the group nor did average concentrations of functional markers apolipoprotein C2 (P = 0.73) and apolipoprotein C3 (P = 0.74). S(v) was low in most (82%) of the adults and was significantly (P < 0.05) associated with age, fasting triacylglycerol, triacylglycerol AUC, and fasting nonessential fatty acids. Significant associations were also observed between S(v) and single nucleotide polymorphisms in 7 genes (APOA1, IL1α, IL1β, TLR4, TCF7L2, CCK1Rec, and STAT3) after correction for phenotypic differences. CONCLUSIONS: This work showed that the within-person variability in postprandial lipemic response is low in most healthy adults. It also showed that variability in this response is associated with a defined set of phenotypic and genotypic characteristics. This trial was registered at clinicaltrials.gov as NCT01172951.