Abstract Background Clostridioides difficile infection CDI is a risk factor for bloodstream infection BSI Fecal microbiota transplantation FMT is more effective than antibiotics in treating recurrent CDI but its efficacy in preventing CDI-related BSI is uncertain Objective To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics Design Prospective cohort study Patients treated with FMT and those treated with antibiotics were matched on propensity score Patients 290 inpatients with recurrent CDI 57 patients per treatment in matched cohort Measurements The primary outcome was primary BSI within 90 days Secondary outcomes were length of hospitalization and overall survival OS at 90 days Results Of the 290 patients 109 were treated with FMT and 181 received antibiotics Five patients in the FMT group and 40 in the antibiotic group developed BSI Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics including number of recurrences and CDI severity comparative analyses were limited to the matched cohort Risk for BSI was 23 percentage points 95 CI 10 to 35 percentage points lower in the FMT group the FMT group also had 14 fewer days of hospitalization CI 9 to 20 fewer days and a 32 percentage point increase in OS CI 16 to 47 percentage points compared with the antibiotic group Limitation Nonrandomized study with potential for unmeasured or residual confounding limited generalizability of the propensity score matched cohort Conclusion In a propensity score matched cohort patients with recurrent CDI treated with FMT were less likely to develop primary BSI