INTRODUCTION: Clostridioides difficile (CDI) is a spore-forming, toxin-producing, gram positive bacteria that can colonize the colon when the normal flora is disrupted causing colitis. However, it can rarely colonize the small intestines causing enteritis, especially in patients with recent antibiotic use, on immunosuppression or have surgically altered intestinal anatomies. CASE DESCRIPTION/METHODS: A 77-year-old female with a history of fulminant CDI colitis requiring subtotal colectomy with end ileostomy presented with abdominal pain and increase in ileostomy output two months after surgery. Her ileostomy drainage tested positive for CDI by PCR and she was started on oral vancomycin for CDI enteritis with resolution of her symptoms. Over the next year, she had multiple recurrences of her CDI that failed vancomycin, fidaxomicin and IV immunoglobulin (IVIG). She eventually had fecal microbiota transplantation (FMT) with stool infused into the proximal jejunum. Her symptoms improved initially, however recurred and her ileostomy drainage tested positive for CDI again. She had a total of four FMT due to recurrence. After her fourth FMT, her symptoms recurred, however; she tested negative for CDI this time. Infectious diarrhea as well as celiac disease were negative and her symptoms did not improve with antidiarrheal agents. She developed significant anxiety and requested to be placed on vancomycin understanding the risks of long-term use of antibiotics. She was started on a prophylactic daily dose of oral vancomycin 125 mg which helped to improve her symptoms. DISCUSSION: CDI enteritis is rare; yet, its incidence is rising. Diagnosis is made both clinically and biochemically by testing for CDI toxin by PCR. In the literature, there are no prospective studies on the treatment of CDI enteritis except for a few case reports. Oral metronidazole has been used, with oral vancomycin used for refractory cases. In our case, the patient failed vancomycin, fidaxomicin, IVIG and three FMT with recurrence of the symptoms after the fourth one. Prophylactic oral vancomycin was started on the patient's request and she noticed improvement in her symptoms. Prophylactic vancomycin has been effective in preventing recurrence of CDI in patients with a history of CDI being treated with oral antibiotics. Our case is unusual given the ongoing symptoms in a PCR negative CDI state. Further research is needed in patients with refractory CDI enteritis with analysis of their bowel flora to better understand this disease and how to treat it