In 1951, using the Uppsala University cyclotron, Leksell and the physicist and radiobiologist Borje Larsson, developed the concept of Radiosurgery. Leksell and Larsson first employed proton beams coming from several directions into a small area into the brain, in experiments in animals and in the first treatments of human patients. Thus, he achieved a new non-invasive method of destroying discrete anatomical regions within the brain while minimizing the effect on the surrounding tissues.

In 1961 he succeeded  as  & Chairman of Neurosurgery at Karolinska institute and perused his work on Stereotactic Radiosurgery and refinement of Stereotactic methods. First prototype of Gamma Knife was installed in Sophiahemmet in 1968.

Today, Leksell's technique is used as an effective treatment for many conditions such as arteriovenous malformations, pituitary tumors, acoustic neuromas, craniopharyngiomas, Meningioma, Matastatic and skull base tumors, and primary brain tumors. The Gamma Knife is manufactured by Elekta Instruments, Inc., a Swedish company which manufactures Stereotactic surgery and Radiosurgery equipment, based on the inventions of Lars Leksell. It was founded by him in 1972.