Ulcerative colitis (UC)-associated pan-enteritis is a newly identified clinical entity that occurs almost exclusively after colectomy. Characterized by diffuse small bowel mucosal inflammation not compatible with Crohn's disease, the optimal treatment modality for this condition is unknown. Tacrolimus is a potent calcineurin inhibitor that has been successfully used in the treatment of UC. We describe a case of severe refractory pan-enteritis after colectomy for UC that was successfully treated with oral tacrolimus after failing intravenous corticosteroid treatment. Tacrolimus may be a safe and effective treatment modality for diffuse enteritis after colectomy in UC patients.