Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome.This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created two pairwise comparisons: mrCDI versus non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs. mrCDI without FMT.We found no significant association between mrCDI (vs. non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR)=1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR=0.86; 0.47-1.56), psoriasis (HR=0.72; 0.23-2.27), diabetes (aHR=0.97; 0.67-1.40), hypertension (aHR=1.05; 0.76-1.44), myocardial infarction (aHR=0.82; 0.63-1.06), stroke (aHR=0.83; 0.62-1.12), or irritable bowel syndrome (HR=0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs. mrCDI without FMT) and diabetes (aHR=0.92; 0.27-3.11), hypertension (aHR=1.41; 0.64-3.15), stroke (aHR=1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR=0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR=1.68; 1.01-2.81).Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.