The present invention is directed to an improved guard for a medical cartridge, such as a unit dose syringe or ampule, comprising a body for receiving the cartridge, and a shield slidably attached to the body. In one form, the guard includes only two parts which are preassembled and ready to receive a cartridge having its own plunger. The body has locking detents which permanently hold the cartridge in the guard, and has cooperating detents and detent pockets which allow the shield to be directed distally, from an unguarded position in which the needle on the cartridge is uncovered for delivery of medication, to a guarded position in which the needle is permanently covered for disposal. In a second form, the guard also includes a plunger assembly for a cartridge not having its own plunger. The plunger assembly is locked onto the body, permanently holding the cartridge received therein. The parts of the device are preferably molded from plastic and may be clear or of a color, such as a latex color or skin tone.