||Background: Dietary dextrose and fructose may promote vascular inflammation and endothelial dysfunction. In certain infant populations, altered postprandial mesenteric hyperemia (PPH) may increase risk for feeding intolerance. Objective: To compare superior mesenteric artery (SMA) PPH following feeds of lactose-containing (LC) formula vs lactose-free (LF; dextrose + sucrose) formula. Methods: In a 2 × 2 crossover study with 6 term newborns, 3 received LC first followed by LF 3 hours later. The remaining 3 received the reverse order. Ultrasound measures of pre- and postprandial SMA flow, diameter, and resistance were taken 5 minutes preprandial and 10, 30, and 40 minutes postprandial. Results: Mean ± SD age and weight (n = 6) were 24.1 ± 2.3 hours and 3.1 ± 0.21 kg. Formula intake was similar for LC and LF (22.5 ± 2.8 mL and 25 ± 1.8 mL, respectively; P = .076). Both formulas increased SMA flow at 10 and 30 minutes. However, postprandial flow was greater for LC overall (P = .004) and especially at 30 minutes (LC 103 mL/min, 52% increase vs LF 92.7 mL/min, 31% increase; P = .014). For both formulas, vasodilation was seen at 10 and 30 minutes and was overall significantly greater following LC than following LF (9.1% vs 6.5%; P = .028). Both formulas elicited significant decreases in SMA vascular resistance over the 10- to 30-minute period (overall P = .016). However, decreases did not differ across formulas (P = .672). Conclusions: The LC formula elicited a greater SMA PPH response than did LF. SMA flow for both formulas was within normal limits; thus, differences are likely inconsequential for a term newborn. However, in a vulnerable preterm infant, differences may become significant.