Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF.With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5–20-μg/kg/day GLP-2 for 3 days (phase 1), and if tolerated continued for 42 days (phase 2). Nutritional therapy was by primary caregivers, and follow-up was to one year.Six patients were enrolled, age 5.4 ± 3.2 months, bowel length: 27 ± 12% of predicted, PN dependent (67 ± 18% of calories). GLP-2 did not affect vital signs, nor were there significant adverse events during the trial. Dosing 5 μg/kg/day gave GLP-2 levels of 52–57 pmol/L, with no change in half-life or endogenous GLP-2 levels. Enteral feeds, weight, Z scores, stooling frequency, and citrulline levels improved numerically. The trial was discontinued early because of a drop in potency.GLP-2 was well tolerated in infants, and pK was similar to children with no changes in endogenous GLP-2 release. The findings suggest that GLP-2 ligands may be safely used in infants and may have beneficial effects on nutritional status. Further study is required.2b Prospective Interventional Study.