OBJECTIVES: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections, which can be challenging to treat with excess morbidity and mortality compared to antimicrobial-susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst faecal microbiota transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety, and efficacy. METHODS: Population: Patients with invasive infection with extended-spectrum beta-lactamase (ESBL-) or carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage. INTERVENTION: Three doses of encapsulated lyophilised FMT. COMPARATOR: Matched placebo capsules. OUTCOMES: Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis. RESULTS: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT, but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups, with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p = 0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p = 0.05) and change in strain dominance within MDRO at the species-level. CONCLUSIONS: Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.