Abstract: An instrument for applying clips in surgery having an operating handle with operating components and a removable clip cartridge with clip applying mechanism. The handle operating components generate reciprocal linear motion imparted to the clip applying mechanism and accommodate rotation of the cartridge about a cartridge axis. An anti-backup mechanism constrains operating components to complete first and second strokes of reciprocal linear motion. The clip applying mechanism actuated by received reciprocal motion applies a clip in surgery, isolates the next clip, and prepares for loading the isolated clip into the jaws on a first stroke, and on the second stroke, opens the jaws and pushes the isolated clip into the open jaws.