Oral exposure to dietary fat results in an early initial spike, followed by a prolonged elevation, of serum triglycerides in humans. The physiological and pathophysiological implications remain unknown. This study sought to determine the incidence of the effect, the required fat exposure duration, and its reliability. Thirty-four, healthy adults participated in 4-6 response-driven trials held at least a week apart. They reported to the lab after an overnight fast, a catheter was placed in an antecubital vein and a blood sample was obtained. Participants then ingested 50 g of safflower oil in capsules with 500ml of water within 15 minutes to mimic a high fat meal, but without oral fat exposure. Blood was collected 0, 10, 20, 30, 40, 50, 60, 120, 240, 360 and 480 minutes after capsule ingestion, with different forms (full-fat, non-fat, none) and durations of oral fat exposures (10 seconds, 5 minutes, 20 minutes and/or 2 hours). A triglyceride response (increase of triglyceride >10mg/dl within 30 minutes) was observed in 88.2%, 70.5% and 50% of participants with full-fat, non-fat and no oral exposure, respectively. Test re-test reliability was 75% with full-fat exposure, but only 45.4% with non-fat exposure. Full-fat and non-fat exposures led to comparable significant elevations of triglyceride over no oral stimulation with 10 second exposures, but full-fat led to a greater rise than non-fat with 20 minutes of exposure. These data indicate nutritionally-relevant oral fat exposures reliably elevate serum triglyceride concentrations in most people.