INTRODUCTION: Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea with high morbidity and mortality, particularly in cases of fulminant disease. Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating severe and refractory CDI, typically administered via colonoscopy. However, in cases complicated by toxic megacolon, alternative methods of FMT delivery may be necessary. CASE REPORT: This case report describes a 46-year-old female with cirrhosis and fulminant CDI complicated by toxic megacolon. Due to the patient's hemodynamic instability and contraindications to endoscopic FMT delivery, a novel approach of nasogastric FMT administration was utilized. The patient received a combination of enema-delivered and nasogastric FMT alongside standard antibiotic therapy. This approach resulted in rapid clinical improvement, with resolution of toxic megacolon, normalization of inflammatory markers, and avoidance of colectomy. DISCUSSION: This report highlights the successful use of nasogastric FMT in a patient with fulminant CDI, offering a potential alternative delivery route when colonoscopic administration is contraindicated. To our knowledge, this is the first reported case of nasogastric FMT successfully resolving -associated toxic megacolon.