Abstract Purpose Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. Methods In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. Results Postprandial concentrations of triacylglycerol (diet-effect: − 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: − 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC_{0–8 h}) and first meal (iAUC_{0–4 h}) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC_{4–8 h}) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC_{0–8 h}, dAUC_{0–4 h}, and dAUC_{4–8 h} for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC_{4–8 h)} tended to be lower after stearic-acid intake (p < 0.10). Conclusion Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.