The unit was established as the 375th Troop Carrier Wing in June 1949 at Greater Pittsburgh Airport, PA as a Reserve unit operating C-46s and C-82s alongside a mix of trainer types. The wing was called to active duty in October 1950 and stationed at Greenville AFB, SC (later Donaldson AFB) until July 1952 when it returned to Reserve status. The unit converted to C-119s before inactivating in November 1957. The 375th reactivated as an Aeromedical Airlift Wing at Scott AFB in January 1966, replacing the 1405th Aeromedical Transport Wing. The unit operated C-118As and C-131As from 1966, plus the C-121G in 1968 when the Pennsylvania ANG was mobilized. The former two types were replaced by the C-9A in 1968. In April 1975 the wing gained responsibility for numerous VIP squadrons and detachments located across the USA. These dets and squadrons were formerly assigned to the major commands to provide transportation for senior officers and were equipped with the CT-39A, but converted to C-12F and C-21A in 1984 and 1985. The squadrons and detachments were subsequently reallocated to the host commands.