The GAU-12 25MM six-barrel gun pod can be mounted on the centerline of the Marine Corp's AV-8 Harrier. It has a 300 round capacity with a lead computing optical sight system (LCOSS) gunsight. The Marines use a 25mm depleted uranium [DU] round in the GAU-12 Gatling gun on AV-8 Harriers.

The Air Force Special Operations Command AC-130U Spectre gunship gunship represents a major-advancement over the two previous generation gunships, the AC-130A and the AC-130H. Changes include enhancement and expansion of its attack sensor suite allowing the aircraft's electro-optic sensors and the All Light Level Television and Infrared Detection System to provide a full 360-degree field of vision; an APG-180 Strike Radar that will allow tracking of both fixed and moving targets through adverse weather; an adjustable GAU-12 25 mm Gatling gun and a Dual Target Attack mode which will allow the AC-130U to strike two targets simultaneously. Alliant Techsystems, Incorporated, Hopkins, Minnesota, manufactures rounds of 25 millimeter high explosive incendiary ammunition applicable to the GAU-12 autogun on the AC-130U aircraft.

In October 1983 the US Army Air Defense Board completed an evaluation of the US Army Armament Research and Development Center (ARDC) air defense gun/missile experiment known as ADGILE. The prototype of the hybrid system consisted of a 25mm GAU-12/U cannon and an engineering ATAS STINGER launcher. The experiment clearly demonstrated the feasibility of an integrated STINGER/gun hybrid system. In February 1985 The USMC evaluated their Light Armored Vehicle-Air Defense System at Eglin Air Force Base (AFB), Florida, using a 25mm GAU-12 cannon and an ATAS launcher.

The LAV-AD light armor vehicle air-defense variant features the Blazer turret, which includes a forward-looking infrared targeting sight, a laser rangefinder, and the option of employing either Stinger missiles or the rapid-fire GAU-12/U 25mm Gatling gun. Its primary mission is to provide low altitude air defense at ranges within the envelope of the Stinger Missiles and the 25mm ammunition. A secondary mission is to provide ground defense against light armored mechanized forces.