 Hughes began work as a junior medical resident officer at the Royal Melbourne Hospital in 1943.Between 1946 and 1949 he occupied various positions in Oxford and London whilst studying for his Fellowship of the Royal College of Surgeons of England (FRCS) and then in 1950 he resumed work in Australia as an assistant surgeon at the Royal Melbourne Hospital and the Royal Children's Hospital in Melbourne.Variously described as "brilliant", a "surgeon of international repute" "one of the most brilliant surgeons and surgical teachers in Australia", a "world-leader in the field of colorectal surgery" and "one of the most distinguished Australian surgeons of the second half of the twentieth century", Hughes was appointed in 1974 as Professor of Surgery at Monash University, a position he retained until 1984.