An interchangeable shaft assembly for use with a surgical instrument. The surgical instrument may include a frame that operably supports a plurality of drive systems and defines an actuation axis. The shaft assembly may comprise a first shaft that is configured to apply first actuation motions to a surgical end effector that is operably coupled thereto. A proximal end of the first shaft is configured to be operably releasably coupled to a first one of the drive systems supported by the frame in a direction that is substantially transverse to the actuation axis.