The authors evaluated historical patterns in the types of procedures performed in diagnostic and therapeutic nuclear medicine and the associated radiation safety practices used from 1945–2009 in a sample of U.S. radiologic technologists. In 2013–2014, 4,406 participants from the U.S. Radiologic Technologists (USRT) Study who previously reported working with medical radionuclides completed a detailed survey inquiring about the performance of 23 diagnostic and therapeutic radionuclide procedures and the use of radiation safety practices when performing radionuclide procedure-related tasks during five time periods: 1945–1964, 1965–1979, 1980–1989, 1990–1999, and 2000–2009. An overall increase in the proportion of technologists who performed specific diagnostic or therapeutic procedures was observed across the five time periods. Between 1945–1964 and 2000–2009, the median frequency of diagnostic procedures performed substantially increased (from 5 wk−1 to 30 wk−1), attributable mainly to an increasing frequency of cardiac and non-brain PET scans, while the median frequency of therapeutic procedures performed modestly decreased (from 4 mo−1 to 3 mo−1). Also a notable increase was observed in the use of most radiation safety practices from 1945–1964 to 2000–2009 (e.g., use of lead-shielded vials during diagnostic radiopharmaceutical preparation increased from 56 to 96%), although lead apron use dramatically decreased (e.g., during diagnostic imaging procedures, from 81 to 7%). These data describe historical practices in nuclear medicine and can be used to support studies of health risks for nuclear medicine technologists.