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Background: Transgastric endoscopy may represent a viable platform for diagnostic and therapeutic pancreatic interventions with reduced morbidity. In a human cadaver model, we aimed to determine the feasibility of transgastric endoscopic access to the lesser sac, creation of an adequate working space within the lesser sac, and reliable identification of lesser sac anatomic structures. Methods: In six human cadavers, endoscopic guidance was used to determine an appropriate access site to the lesser sac. Subsequently, endosonographic guidance was used to introduce an aspiration needle into the potential space between the stomach and the pancreas. After creating a fluid cushion and dilating the needle tract, an endoscope was advanced through the gastrotomy into the lesser sac and air insufflation was used to create a working space. Predetermined anatomic structures were systematically sought and marked when recognized. In the final two cadavers, endoscopic closure of the access site was performed. Results: All six procedures were successful in achieving access to the lesser sac and establishing an adequate working space. The access sites appeared amenable to endoscopic closure. Reliable organ identification, however, was not achieved in all cases, representing one of the immediate barriers to clinical application. Conclusions: Transgastric endoscopic access to the lesser sac can be achieved reliably and an adequate working space can be established. Additional research addressing endoscopic orientation and organ recognition within the lesser sac is necessary. The immediate potential applications of this approach include differentiating benign from malignant pancreatic pathology. [ABSTRACT FROM AUTHOR]