He then worked as a virologist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia and at the Virus Research Institute at Entebbe, Uganda. He returned to Australia to work in the School of Microbiology at the John Curtin School of Medical Research. Cairns took a sabbatical to research at the Cold Spring Harbor Laboratory between 1960 and 1961, and returned there to serve as the director from 1963 to 1968.
After his work in Australia, he continued his career as a virologist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and the Virus Research Institute in Entebbe, Uganda. He returned to Australia to work at the School of Microbiology at the John Curtin School of Medical Research. Cairns took a sabbatical from 1960 to 1961 to conduct research at the Cold Spring Harbor Laboratory, returning there as director from 1963 to 1968.