INTRODUCTION: Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis. METHODS AND ANALYSIS: In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function. ETHICS AND DISSEMINATION: The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov study identifier NCT04932577.