On February 21, 1966, the 3-1-5 was reactivated and redesignated, this time as the 315th Air Commando Wing, Troop Carrier. The 315th ACW, TC was assigned to the 315th Air Division (Combat Cargo), just as it had been when the 315 TCW was deactivated back in 1955. On March 8, 1966, the 315th ACW, TC was organized and stationed at Tan Son Nhut Air Base, South Vietnam. Subsequently, the Wing was attached to the 2nd Air Division throughout the remainder of March and then was further reassigned to the 7th Air Force on April 1, 1966 until October 15, 1966.
From March 8, 1966 up until October 15, 1966, the 315th ACW, TC maintained responsibility for all of the airlift requirements that were needed in the Republic of Vietnam (South Vietnam). These missions included the control over all United States Air Force airlift assets, Aerial Port Squadrons, an Aeromedical Evacuation Squadron, and a special air transport flight of the Royal Australian Air Force.
After October 15, 1966, the 315th ACW, TC engaged in C-123 airlift operations throughout Vietnam. These operations included the aerial movement of troops and cargo, flare drops, Aeromedical Evacuation, and airdrops of crucial supplies and paratroops. One other noteworthy mission the Wing was tasked with was Ranch Hand, the systematic defoliation of the thick jungles and forests that the Viet Cong used for concealment and cover. The herbicide was delivered with specially modified versions of the Fairchild C-123 Provider, known as the UC-123. Ranch Hand UC-123s were also used to spray insecticides on crops in Thailand to help combat a plague of locusts.
On August 1, 1967, the 315th ACW, TC was redesignated as the 315th ACW and exactly one year later, the Wing was redesignated again, this time as the 315th Special Operations Wing.
The 315th ACW, TC moved to Phan Rang AB, South Vietnam on June 15, 1967 and remained there until the deactivation of the 3-1-5 in 1972. From PRAB, the 3-1-5 helped to train C-123 aircrews for the South Vietnamese Air Force and the Wing gained control over close air support missions flown by Cessna A-37 Dragonfly aircrews. In 1971, as the 315th Tactical Airlift Wing, the Wing expanded its mission with the added responsibility of the control of the interdiction operations being conducted by the 8th Special Operations Squadron and the psychological warfare and visual reconnaissance operations of the 9th SOS.
On 1 January 1970, effective with a new re-designation, the 315th SOW became the 315th TAW and remained that way until the Wing’s deactivation on March 31, 1972.