Surgical clamping and cutting instruments are disclosed. In one aspect, a surgical instrument comprises an elongate shaft with an end effector having first and second jaws, a release member movably coupled to the end effector and a drive member configured to translate relative to the end effector. The instrument further includes a locking member movable from a first position permitting distal translation of the drive member, to a second position preventing distal translation of the drive member. The locking member moves into the second position after the drive member has been driven distally. This inhibits or prevents hazardous actuation of a knife or drive beam when, for example, there is a spent or previously fired cartridge in place.