In 1959, he wrote two influential articles in Science: "Reasoning Foundations of Medical Diagnosis" (with Lee B. Lusted) and "Digital Electronic Computers in Biomedical Science". Both articles encouraged biomedical researchers and physicians to adopt computer technology. In 1960 he established the National Biomedical Research Foundation (NBRF), a non-profit research organization dedicated to promoting the use of computers and electronic equipment in biomedical research. At the NBRF Ledley pursued several major projects: the early 1960s development of the Film Input to Digital Automatic Computer (FIDAC), which automated the analysis of chromosomes; the invention of the Automatic Computerized Transverse Axial (ACTA) whole-body CT scanner in the mid-1970s; managing the Atlas of Protein Sequence and Structure (created in 1965 by Margaret O. Dayhoff); and the establishment of the Protein Information Resource in 1984. Ledley also served as editor of several major peer-reviewed biomedical journals. In 1990, Ledley was inducted into the National Inventors Hall of Fame. He was awarded the National Medal of Technology in 1997. He retired as president and research director of the NBRF in 2010.

Ledley is most widely known for his 1970s efforts to develop computerized tomography (CT) or CAT scanners. This work began in 1973, when the NBRF lost most of its NIH funding due to federal budget cuts. During this time, the NBRF had also become increasingly involved in on-campus computing projects. Quickly trying to raise enough funds to cover the NBRF employee salaries, Ledley looked for projects the organization could undertake for Georgetown University. After learning that Georgetown research physicians were frustrated by the $500,000 cost of a CT scanner they wished to buy from EMI (EMI-Scanner), Ledley promised them that the NBRF could build a similar machine for only half the price. The university agreed to give Ledley a chance, and for the next several months a team led by Ledley, Golab, Wilson, and Frank Rabbitt, worked to develop a prototype.

As the use of CT scanners became widespread, Ledley rose to considerable prominence. The ACTA prototype was displayed at the Smithsonian’s National Museum of American History, in Washington, D.C.. The Smithsonian also established an archive for materials related to the development of ACTA. For his role in developing ACTA, Ledley was inducted into the National Inventors Hall of Fame in 1990 and was awarded the National Medal of Technology and Innovation in 1997.

According to wikipedia