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A 39-year-old male with a large symptomatic tubulovillous adenoma of the first and second portion of the duodenum was initially managed by endoscopic submucosal resection (EMR). The majority of the adenoma was excised by EMR in two stages. However, follow up endoscopy revealed persistent adenoma with regrowth to about 30% circumferential involvement of the duodenum and proximity to the ampulla. A laparoscopic trans-duodenal local resection was then performed with primary repair of the medial and lateral duodenum avoiding a pancreaticoduodenectomy with excellent oncologic and clinical results.