Ledford has held positions as a Clinical Professor at the Uniformed Services University of the Health Sciences (USUHS), the medical school operated by the armed forces and at the University of Texas Health Science Center at San Antonio.

His tenure as Surgeon General came at the time of the Gulf War, when Allied forces liberated the Kuwait after Iraq invaded the country in 1991.

This period was also marked by the difficulties in organizing military medical assets to the Persion Gulf region, which led to calling of reservists in the United States.

[6][7] The SFBR is an independent medical research institution with close ties, but a separate administration, with the University of Texas Health Science Center at San Antonio.

He also created the Lieutenant General Frank Ledford Award, annually recognizing the most outstanding post-graduate US Army PA who successfully completes a PhD or DSc program and engages in research.