BACKGROUND: infection (CDI) causes high morbidity and mortality. Faecal microbiota transplantation (FMT) is well-established for CDI, but therapeutic strategies may be optimised. We aimed to evaluate clinical outcomes by analysing therapeutic strategies in a real-life cohort of patients with CDI treated with FMT. METHODS: We conducted a multi-site cohort study, including 1170 patients with CDI, treated with FMT through capsules, colonoscopy, or nasojejunal tube between May 2016 and December 2023. The primary outcome was cure of associated diarrhea (CDAD) eight weeks after treatment. We investigated antibiotic pretreatment type and length, FMT dosing and administration, and post-FMT prophylactic vancomycin during non-CDI antibiotic use, applying multivariable mixed-effect regression analysis including the patient as a random effect. The study was preregistered at ClinicalTrials.gov, NCT03712722. FINDINGS: The 1170 patients received 1643 FMT treatments. Patients' median age was 71 years (interquartile range 56-80 years). Following their first FMT treatment, 699 patients (60% (95% confidence interval: 57-63%)) were cured of CDAD. After repeated FMT treatments, 944 patients (81% (78-83%)) were cured. Prolonged antibiotic pretreatment was associated with higher cure rates (65% (59-70%), odds ratio (OR): 1.22 (1.10-1.36), p < 0.001). FMT administration through oral, multi-dose capsules (69% (63-74%), OR: 1.19 (1.11-1.27), p < 0.001) or colonoscopy (69% (61-76%), OR: 1.14 (1.04-1.24), p = 0.01) resulted in the highest cure rates. Neither antibiotic pretreatment type nor prophylactic vancomycin during non-CDI antibiotics affected cure rates. In patients for whom FMT was initially unsuccessful, repeated FMT was more effective than antibiotic treatment alone. INTERPRETATION: CDI outcomes could be improved by optimising antibiotic pretreatment duration, selecting appropriate FMT delivery methods, and repeating FMT. FUNDING: Innovation Fund Denmark (j.no. 8056-00006B).