The present invention is directed to a system for closing a defect in a tissue wall, comprising an elongate member defining a working lumen therethrough having a lumen diameter, and a flexible plug member having a distal portion, a proximal portion, and an elongate middle portion intercoupling the proximal and distal portions, wherein the distal and proximal portions both have an unconstrained outer diameter that is larger than the lumen diameter, and wherein the elongate middle portion has an unconstrained outer diameter that is smaller than the lumen diameter. The flexible plug member distal, middle, and proximal portions are configured to be advanced through the working lumen with the distal portion in a collapsed state to a position wherein the distal portion exits the working lumen and expands to an expanded configuration wherein it may be urged against the defect in the tissue wall to substantially occlude the defect. Moreover, upon subsequent retraction of the elongate member relative to the flexible plug member, the proximal and middle portions exit the working lumen to form a configuration such that an expanded state of the proximal portion maintains the position of the distal portion relative to the defect in the tissue wall.