Following graduation from medical school, Jaffe completed a residency in internal medicine at UCLA Hospital.

After three years at the CDC, he left to complete an infectious diseases (ID) fellowship at the University of Chicago Medical Center.

[1][3][4][5] Jaffe returned to the CDC in 1981 as an Epidemic Intelligence Service officer and began working to find the cause of AIDS, a then-unnamed disease.

[5] This work was featured in And the Band Played On, a 1987 book by Randy Shilts about the early days of the disease.

[5][7] In 2004, Jaffe left the CDC to become a professor and head of the Department of Public Health at the University of Oxford.