Ipilimumab is a monoclonal antibody that works as an immunotherapeutic agent through selective targeting of T cells to strengthen the response to metastatic melanoma. It is well known that this pharmaceutical agent can cause the adverse effect of colitis. We report a rare presentation of ileocolitis refractory to both glucocorticosteroids and infliximab with a resultant pneumatosis and perforation requiring subtotal colectomy and end ileostomy.