Inclusion Criteria:  Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation History of at least one episode of overt HE any time in the past Prescribed both lactulose and rifaximin, and compliant with this treatment  Exclusion Criteria:  Current episode of overt HE Variceal bleeding in the last 4 weeks Gut-absorbable or intravenous antibiotic therapy in the last 28 days Fecal microbiota transplant in the last 6 months Use of probiotics in the last 2 weeks Alcohol or illicit drug intake in the last 4 weeks Primary sclerosing cholangitis as etiology of liver disease History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis Prior diagnosis of dementia or other primary neurocognitive disorder Known hypersensitivity/allergy/intolerance to Vancomycin and any ingredients of VE303: sucrose, histidine, yeast extract, cysteine, metabisulfite, and microcrystalline cellulose History of Roux-en-Y Gastric bypass Any gastrointestinal surgery in the last year Substantial immune compromise/deficiency (e.g., uncontrolled human immunodeficiency virus, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia) Pregnancy or breast feeding Model for end-stage liver disease (MELD) > 20 History of spontaneous bacterial peritonitis Hemodialysis in the last 28 days Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt in the last 3 months (permissible if placed >3 months before enrollment) Unstable doses of opiates, benzodiazepines or other sedating medication Chronic methadone or low dose benzodiazepines (for example) is acceptable