Introduction: Ipilimumab (Yervoy) is an anti-CTLA-4 antibody recently approved for treatment of metastatic melanoma, and has led to the improvement in survival rates worldwide. However, its use may lead to immune-related adverse effects (irAEs), which comprise rash, pruritus, diarrhea, colitis, hepatitis, and hypophysitis. We present 3 recent cases that represent a wide spectrum of Ipilimumab gastrointestinal irAEs. Cases: First case of 89-year-old female with recurrent malignant melanoma of left foot on ipilimumab (3 mg/kg, 4 cycles) presented with weakness and progressively worsening diarrhea, 2-6 watery bowel movements daily with small amount of blood. Patient had WBC 15,000/uL, elevated creatinine at 1.6 mg/dL, fecal WBCs >25/hpf, negative C. difficile stool antigen and toxin, and negative stool cultures. Severe colitis was seen on colonoscopy with histological confirmation of autoimmune colitis, and patient was initiated on prednisone (50 mg tapered over 10 days), with no improvement rising concern about steroid-resistant colitis. At this point Infliximab therapy (5 mg/kg) was started with resolution of diarrhea. Second case of 88-year-man also had similar presentation, but responded well to steroids with resolution of diarrhea due to early recognition and constituted steroid-responsive autoimmune colitis. Third case of 51-year-old man with malignant melanoma, currently on ipilimumab (3 mg/kg, 2 cycles), presented with nausea/vomiting, diarrhea, and severe abdominal pain for 1 week. Infectious work-up was all negative. Sigmoidoscopic evaluation revealed severe colitis; prednisone (50 mg tapered over 10 days). Bowel perforation was suspected and confirmed on acute abdominal series. Patient underwent emergent laparotomy with right hemicolectomy and ileostomy. Patient recovered after an extended hospital stay. Discussion: Ipilimumab-induced autoimmune colitis is becoming a more frequent entity among patients treated for metastatic melanoma. Currently, first line approach is a 4-6 weeks steroid taper (starting oral prednisone 1-2 mg/kg daily or dexamethasone 4 mg every 4 hours), which leads to a significant improvement of symptoms within 1-2 weeks. Infliximab is a second line salvage therapy and used for steroid-resistant cases. Given the limited number of cases reported there are no formal guidelines on when to start infliximab and more information is needed in order to prevent complications as perforation and hemorrhage. Our case series intends to make practicing gastroenterologists cognizant regarding this emerging entity, and also urge them to maintain a high suspicion for possible complications (perforation) in patients started on steroids for this autoimmune colitis.