Much of the work done by perioperative nurses focuses on patient safety. Perioperative nurses are aware that unreported near misses occur every day, and they use that knowledge to prioritize activities to protect the patient. The purpose of this study was to identify the highest priority patient safety issues reported by perioperative RNs. We sent a link to an anonymous electronic survey to all AORN members who had e-mail addresses in AORN’s member database. The survey asked respondents to identify top perioperative patient safety issues. We received 3,137 usable responses and identified the 10 highest priority safety issues, including wrong site/procedure/patient surgery, retained surgical items, medication errors, failures in instrument reprocessing, pressure injuries, specimen management errors, surgical fires, perioperative hypothermia, burns from energy devices, and difficult intubation/airway emergencies. Differences were found among practice settings. The information from this study can be used to inform the development of educational programs and the allocation of resources to enhance safe perioperative patient care.