Alagill syndrome (ALGS) is a genetic disorder of the liver causing cholestasis and pruritus in which ileal bile transporter inhibitors such as maralixibat help control pruritus. The article describes two cases of patients with ALGS treated with maralixibat. In the first case of a 10-day-old newborn with cholestasis, jaundice, acholic stools, and a JAG1 mutation, pruritus, serum bile acids, bilirubin, and cholesterol were significantly improved after treatment; biopsies at 13 months showed regression of fibrosis from cirrhosis to F2 stage, decreased liver stiffness, splenomegaly, and increased platelet count. In the second case of a 15-year-old female with moderate portal hypertension and mild pruritus, after 24 months of treatment, the pruritus completely resolved, serum bile acids decreased, liver stiffness and splenomegaly improved, and platelet counts increased. Liver enzymes were mildly elevated in both patients, but treatment was continued without dose adjustment. Findings suggest that maralixibat improves pruritus, reduces bile acids, and has benefit in fibrosis and portal hypertension.