A prosthesis (10) configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis. The prosthesis includes an expandable frame (20) configured to radially expand and contract for deployment within the body cavity, and an outer skirt (30) positioned annularly around an exterior of the expandable frame. The outer skirt can extend outward from the frame and be secured to an outwardly extending anchor (22) on the frame to create an axial barrier to fluid flow exterior to the frame when deployed within the body cavity. The prosthesis comprises an expandable frame, a plurality of distal anchors (24) and a plurality of proximal anchors (22). The anchors extend outwardly from the frame. The frame is configured to radially expand and contract for deployment within a body cavity. The frame and anchors can have one of many different shapes and configurations. For example, when the frame is in an expanded configuration, the proximal anchors can extend a significant distance away from the exterior of the frame, such as a length equal to or greater than about one half the diameter of the frame. As another example, the anchors can have looped ends.
