We report a case of a 50-year-old woman with a non-ampullary duodenal adenoma treated with piecemeal EMR. She was discharged two hours after the procedure but returned ten hours afterward with severe upper gastrointestinal bleeding. Endoscopy showed active bleeding in the post-EMR defect. After hemostasis with a coagrasper, a limited muscularis propria injury was revealed which was clipped. The patient developed abdominal pain, and CT scan demonstrated retroperitoneal air. Persistent pain and melena led to a repeat endoscopy, which exposed a large perforation. Because of friable edges, an over-the-scope clip (OVESCO) was deployed to grasp deeper tissue layers. Follow-up CT scan showed no leak. On day ten, a retroperitoneal collection was successfully drained. One month later the patient was asymptomatic and six-month imaging was normal.