This study was undertaken to determine the prevalence of adverse reactions to positron emitting radiopharmaceuticals as well as to nonradioactive drugs used in interventional nuclear medicine during PET studies. Methods: A prospective 4-yr study was performed with 22 collaborating institutions using a questionnaire, which indicated for each month of the study the number of PET procedures performed, the number of adverse reactions to PET radiopharmaceuticals as well as the number of adverse reactions to interventional nonradioactive pharmaceuticals used for PET. Results: A total of 33,925 radiopharmaceutical doses were recorded in a retrospective examination of records by the 22 participating institutions. In addition, the total prospective number of administered doses recorded by the participants was 47,876, for a total number of positron emitting radiopharmaceutical administrations of 81,801, No adverse reactions were found from any PET radiopharmaceutical dose. There were no deaths or hospitalizations caused by nonradioactive interventional pharmaceuticals used adjunctive to PET studies. Conclusion: PET radiopharmaceuticals have an extraordinary safety record with no adverse reactions reported in over 80,000 administered doses in this study.