INTRODUCTION: Clostridioides difficile infection or C. diff (CDI) is the most common cause of health-care associated diarrhea. Despite interventions directed at decreasing transmission, the incidence of CDI remains high. Its morbidity, mortality, and overall burden on health care necessitate alternative therapies. As such, we report a case of severe CDI successfully treated with intravenous immunoglobulin (IVIG), a pooled blood product primarily used to treat antibody deficiencies or autoimmune diseases. CASE DESCRIPTION/METHODS: An 86-year-old female with diabetes and atrial fibrillation presented to our hospital with bloody stools. Her hospital course was long and complicated, requiring trials of multiple antibiotics: ceftriaxone, metronidazole, piperacillin-tazobactam, and ertapenem. One month into her hospitalization, she became septic with diarrhea and abdominal pain: temperature 101.3 F (38.5 C), white blood cell count 17K, creatinine 0.9 (baseline 0.7), BUN 25, albumin 1.7. Stool was positive for C. diff toxin. Despite 5 days of oral vancomycin, symptoms did not regress. Abdominal computed tomography (CT) imaging revealed pancolitis. Vancomycin was discontinued. Fidaxomicin was started. After 6 days of fidaxomicin, symptoms were unchanged. 25 grams of IVIG was given (347 mg/kg) as an adjunct to fidaxomicin. The next day, her stool count decreased from an average of 9 per day to 5. After once daily 25-gram IVIG treatment for 3 consecutive days, the patient had complete resolution of her abdominal pain and diarrhea. DISCUSSION: Inflammation and disease in CDI are mediated by toxins. Some studies documented poor immune response to C. diff toxins in patients with severe or refractory disease. IVIG addresses this issue, as it contains C. diff antitoxin antibodies that act as passive immunity to neutralize the toxins and help with disease resolution. This report is one of several documenting success with IVIG in severe CDI. However, IVIG use in C. diff is limited, partly due to its high cost but perhaps in larger part due to small-sample retrospective analyses deeming its benefits statistically insignificant. Larger prospective controlled studies investigating different doses, duration, and timing of IVIG therapy are necessary to fully clarify IVIG's role in CDI. Moreover, IVIG may prove to be cost-effective by preventing severe or recurrent disease. In cases of CDI refractory to standard antibiotic treatment, passive immunity with IVIG may be a reasonable adjunct to standard therapy.