Crohn's disease is characterized by inflammation of the mucosal lining of the gastrointestinal tract. Infliximab is a tumor necrosis factor-α inhibitor that has been associated with increased remission and decreased disease flare-ups. Biological agents such as infliximab have been associated with adverse events. We present a rare case of cardiac tamponade caused by infliximab treatment for Crohn's disease in a 30-year-old female. She was treated with emergent pericardial window and drainage of pericardial fluid. Infliximab was discontinued, and serositis was treated with steroids. The patient was later successfully rechallenged with vedolizumab.