Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine. 8 SBS patients with end-jejunostomy and less than 200 cm small intestine were given GLP-2, 1600 μg subcutaneously (SC), or isotonic saline in a double blinded manner. At 0, 30 and 60 min plasma GLP-2 was measured, and from 0 to 90 min, blood flow in the superior mesenteric artery (SMA) and the celiac artery (CA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by continuous impedance cardiography and finger plethysmography. Plasma GLP-2 concentrations increased significantly in the GLP-2 group, whereas no changes were seen in the placebo group. Compared to baseline, GLP-2 SC elicited a 19.4% decrease (p < 0.01) in the resistance index (RI) and a 97.6% increase in time averaged maximal velocity (TAMV) in the SMA (P < 0.01). In the CA there were no significant changes in RI or TAMV in the GLP-2 or placebo group. Blood flow and length of remaining intestine were correlated (RI: y = 0.14 + 4.3, R = 0.83, p = 0.01 and TAMV: y = 1.21 + 21.3, R = 0.63, p = 0.09). GLP-2 non significantly increased cardiac output (CO), stroke volume (SV) and significantly increased heart rate (HR) compared to baseline. Subcutaneous GLP-2 increased SMA blood flow in end-jejunostomy SBS patients with less than 200 cm of remaining small intestine. The increase in blood flow correlated with the length of remaining intestine, suggesting that the increase is coupled to the metabolic actions of GLP-2 on the gut rather than effects on the vasculature. ► Exogenous GLP-2 administration increases mesenteric blood flow in SBS patients. ► Increase in blood flow seems to correlate to the length of remaining small intestine. ► The findings suggest that the increase is coupled to the metabolic actions of GLP-2.