A surgical stapler having a supporting frame, replaceable staple cartridge, an anvil, a mechanism for approximating the cartridge relative to the anvil, and a mechanism for firing the device so as to crimp the staples against the anvil in a manner to enable the surgeon to substantially simultaneously place one or more rows of surgical staples in organs or tissue. The device, while at all times permitting approximation of the cartridge relative to the anvil, provides a novel lockout feature for positively preventing retiring if the staple cartridge is spent. In this way, unlike the prior art devices, the device of the present invention can be used as a clamping mechanism even after the staples have been fired.