Background & aims Individuals with fasting triglycerides (TG) <150 mg/dL can experience a deleterious postprandial TG response ≥220 mg/dL to a high-fat meal (HFM). The purpose of this study was to identify individuals based on fasting TG that would benefit most from additional postprandial screening. Methods We conducted a secondary analysis of 7 studies from our laboratories featuring 156 disease-free participants (64 M, 92 F; age 18–70 years; BMI 18.5–30 kg/m2). Participants observed a 10–12 h overnight fast, after which they consumed an HFM (10–13 kcal/kg body mass; 61–64% kcal from fat). Two methods were used to identify lower and upper fasting TG cut points. Method 1 identified the lower limit as the TG concentration at which ≥90% of individuals presented peak postprandial TG (PPTG) <220 mg/dL and the upper limit as the concentration which ≥90% of individuals presented PPTG ≥220 mg/dL. Method 2 utilized receiver operating characteristic (ROC) curves and identified the lower limit as the fasting TG concentration where sensitivity was ≈95% and the upper limit as the concentration at which specificity was ≈95%. Results In Method 1, 90% of individuals with fasting TG >130 mg/dL (>1.50 mmol/L) exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L), while 100% of individuals with fasting TG <66 mg/dL (0.75 mmol/L) had PPTG that did not exceed 220 mg/dL (2.50 mmol/L). In Method 2, when sensitivity was ≈95%, the corresponding fasting TG concentration was 70 mg/dL (0.79 mmol/L). When specificity was ≈95%, the corresponding fasting TG concentration was 114 mg/dL (1.29 mmol/L). Based on methods 1 and 2, there was a moderate positive association (r = 0.37, p < 0.004) between fasting and PPTG for individuals with fasting TG between 70 and 130 mg/dL (0.79–1.50 mmol/L), in which 24% exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L) while 76% did not. Conclusions Postprandial TG testing is likely most useful for individuals with fasting TG concentrations between 70 and 130 mg/dL (0.79–1.50 mmol/L). Outside of this range, postprandial TG responses are largely predictable. Establishing a specific patient group for which postprandial TG testing is most useful may lead to earlier risk detection in these individuals.