Background The concept of endoluminal therapy for various disease states has gained significant attention. This report describes the authors’ initial animal experience with a novel endoscopic duodenal-jejunal bypass sleeve (DJBS) in a porcine model. The DJBS consists of an implant delivered endoscopically, anchored in the proximal duodenum, and extended into the jejunum. This device aims to mimic the intestinal bypass effects of Roux-en-y gastric bypass without the need for stapling or anastomosis and may offer novel therapeutic benefit for patients with obesity, type 2 diabetes, or both. Methods Five DJBS devices were delivered in five domestic, female Yorkshire pigs. The devices were delivered and retrieved the same day and left in situ for less than 1 h. The animals were kept alive for 4 days after explantation for evaluation of their general health after the procedure. After they were killed, gastric, duodenal, and jejunal tissues were examined and harvested for histologic assessment of any acute device or procedure-related effects. Results Delivery of the implant took an average of 18 min (range, 10–38 min) and required an average fluoroscopy time of 8.1 min (range, 3.8–16.6 min). Retrievals were performed in an average of 7.4 min (range, 5–9 min) using fluoroscopy for an average of 2.3 min (range, 1.3–4.5 min). Followed for 4 days after explantation, the animals were normal and healthy. There were no pathologic findings in the explanted tissue. Conclusions The DJBS can be safely deployed and retrieved endoscopically. Future long-term survival studies are warranted to help define the role of promising technology.