Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low‐glycaemic index isomaltose (Palatinose™)with that of sucrose in modulating EF, as assessed by flow‐mediated dilation (FMD). In this double‐blinded cross‐over study, 80 overweight mildly hypertensive subjects were randomized to receive50 g of either isomaltose or sucrose. On two non‐consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0–T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltose compared to sucrose (ΔFMD = −0.003% and −0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p =0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r‐range = −0.20 to −0.23, p < 0.1). Sub‐analysis suggested a lower FMD in insulin‐resistant (IR) compared to insulin‐sensitive subjects. Isomaltose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltose to preserve the endothelial function postprandially and consequently play a favourable role in cardiovascular health.