A device and method for accessing the interior of a cavity of a patient is described. The transmural access system includes an overtube (110) for use with an endoscope, a safety trocar (500), suture anchors (115), and a suture exchanger (151). The overtube is deployed in conjunction with an endoscope through a selected body passageway of a patient to locate a sight for an access portal. The distal end of the multi-lumen overtube is secured to an interior body wall of the selected access portal. A safety trocar is advanced through the main lumen of the overtube to form the access portal to the body cavity. Upon completion of the desired medical procedure, the access portal can be closed by deploying a suture exchanger.