Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients’ medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68–1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72–1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT.